Studies on the syntheses of heterocyclic compounds. Part 676. Synthesis of 1-substituted 7-methoxymitosenes

摘要

28 J.C.S. Perkin IStudies on the Syntheses of Heterocyclic Compounds. Part 676. tSynthesis of 1 -Substituted 7-MethoxymitosenesBy Tetsuji Kametani,' Kimio Takahashi, Yoshio Kigawa, Masataka Ihara, and Keiichiro Fukumoto,Pharmaceutical Institute, Tohoku University, Aobayama, Sendai, JapanOn treatment with lead tetra-acetate in acetic acid, the 2,3-dihydro-lH-pyrrolol,2-aindoles (4)-(8) were selec-tively acetoxylated a t C-1 to give the acetates (1 3)-(17). Theacetates (1 6) and (1 7) and 1 -acetoxy-2,3-dihydro-7-methoxy-6-methyl-5.8-dioxo-1 H-pyrrolol,2-aindole-9-carbaldehyde (27) were hydrolysed to the correspond-ing alcohols (20), (21), and (28). The alcohols (20) and (21) were oxidised to the l-ketones (22) and (23).and (28) was chlorinated with methanesulphonyl chloride and lithium chloride in dimethylformamide to give1 -chloro-2,3-dihydro-7-methoxy-6-methyl-5,8-dioxo-l H-pyrrolol,2-aindole-9-carbaldehyde(29). On heatingthe acetates (1 3).(1 4). and (1 7) in acetic acid, elimination of acetic acid occurred to yield the 3H-pyrrolol,2-ain-doles (24)-(26).RECENTLY, we reported a convenient synthesis of 2,3-dihydro-lH-pyrrolo 1,2-aindoles, required for a syn-thetic approach to the mitomycins (l).l We now reporta method for introduction of a functional group at C-1in these compounds, an important step in the envisagedsynthesis. Our work provides an alternative route tothe intermediate (16), used by Remers and his co-workers for the synthesis of desammonoapomitomycinA (2),3 and also an alternative synthesis of (26), whichhas been transformed into the tetracyclic compound (3)by Matsui et aL4( 1 1 x Y Z ( 2 )Mitomycin A Me0 Me0 HMitomycin 6 Me0 HO MeMitomycin C NH, Me0 HPorfiromycin NH, Me0 Me( 3 )First, oxidative reactions of the 2,3-dihydro-lH-pyrrolol,2-aindole-9-carbonitriles (4) and (5) wereexamined under several conditions.On treatment with2 mol. equiv. of 2,3-dichloro-5,6-dicyano-l,4-benzo-quinone in methanol at room temperature (4) was un-affected but (5) gave 6-formyl-2,3-dihydro-7-methoxy-1H-pyrrolo 1,2-aindole-9-carbonitrile (9) in 71 yo yield.Treatment of (4) or (5) with N-bromosuccinimide incarbon tetrachloride yielded no bromination product.On the other hand, treatment of (5) with N-bromo-t Part 675, T.Kametani, Y . Kato, T. Honda, K. Fukumoto,J . Amer. Chem. SOC., in the press.succinimide in methanol at room temperature yielded8-bromo-2,3-dihydro-7-me t hoxy-6-me t hyl- 1 H-pyrrolo-1,2-aindole-9-carbonitrile (10) and 8-bromo-2,3-di-hydro-5,7-dimet hoxy-6-met hyl- LH-p yrrolo 1,2-a indole-9-carbonitrile (11) in 29 and 31 yield, respectively.Bromine is presumably introduced first at C-8 (having ahigher electron density than C-5), and compound (11)would then be formed through the adduct (12), byoxidation.Introduction of a substituent at C-1 was achieved byusing lead tetra-acetate. Thus stirring compound (4)or (5) with 1 mol. equiv. of lead tetra-acetate in aceticacid at room temperature afforded the l-acetoxy-compounds (13) and (14) in 76 and 74 yield, re-spectively.However, reactions with 2 mol. equiv. oflead tetra-acetate in acetic acid at 90-100 "C furnishedtarry products, from which 1,8-diacetoxy-2,3-dihydro-6,7-dimethoxy-lH-pyrrolo 1,2-aindole-9-carbonitrile(18) and l-acetoxy-6-acetoxymethyl-2,3-dihydro-7-methoxy-lH-pyrrolo 1,2-aindole-9-carbonitrile (19)were isolated in 11 and 18 yield, respectively.The 2,3-dihydro-lH-pyrrolo 1,2-aindole-9-carbalde-hydes (6) and (7) were then acetoxylated to givecompounds (15) and (16) in 65 and 74 yield, re-spectively, by treatment with 1 mol. equiv. of leadtetra-acetate in acetic acid at room temperature. Theacetate (16) was hydrolysed with hot methanolic 10potassium hydroxide to afford the alcohol (20) in 86yield. Oxidation of the alcohol (20) with activatedmanganese dioxide in methylene chloride yielded 2,3-dihydro-7-methoxy-6-methyl-l-oxo-lH-pyrrolo 1,241-indole-9-carbaldehyde (22) in 74 yield.Refluxing(13) and (14) in glacial acetic acid under nitrogen gavethe SH-py~~olo 1,2-aindoles (24) and (25), identifiedfrom spectra (see Experimental section). Similar treat-ment of (16) gave no olefinic compound but only tarrymaterial. The acetate (16) has already been convertedinto desammonoapomitomycin A (2) in eight steps byRemers and his co-~orkers.~ Heating l-acetoxy-2,3-J. C. Webb, D. B. Cosulich, J. H. Mowat, J. B. Patrick, R. W.Broschard, W. E. Meyer, R. P. Williams, C. F. Wolf, W. Flumor,C . Pidacks. and J. E.Lancaster, J . Amer. Chem. Soc.. 1962, 84,3186.T. Kametani, K. Takahashi, M. Ihara, and K. Fukumoto,J.C.S. Perkin I , 1976, 389.2 D. L. Fost, N. N. Ekwuribe, and W. A. Remers, TetrahedronLetters, 1973, 131; G. Leadbetter, D. L. Fost, N. N. Ekwuribe,and W. A. Remers, J . Org. Chem.. 1974, 39, 3580.T. Hirata. Y. Yamada, and M. Matsui, Tetrahedron Letters,5 J. W. Findlay and A. B. Turner, J . Chem. SOC. (C), 1971,547.A. R. Battersby, M. Ihara, E. McDonald, J. Saunders, and1969, 4107.R. J. Wells, J.C.S. Perkin I, 1976, 2831977di hydro-7-met hox y-6-met hyl-5,8-dioxo- 1 H-pyrrolo- 1,2-aindole-9-carbaldehyde (27), prepared from (16)according to Remers' m e t h ~ d , ~ in acetic acid gaveonly unidentified material. Hydrolysis of (27) with(11)BrU(10)(12)U IAcO(19)(17) R ' = Me, R2= C02Me 1(20) R = CHO (22) R = CHO(21) R = C02Me (23) R =C02Me 10(24) R' = OMe, R2 = CN125) R' = Me, R2= CN(26) R ' = Me, R2= C02amp;(27) R = OAC(28) R = OH(29) R = CImethanolic potassium hydroxide as in the case of (20)yielded no alcohol (28), whereas stirring (27) withaqueous methanolic sodium hydrogen carbonate atroom temperature afforded the alcohol (28) in 95 yield.Stirring the alcohol (28) in dry dimethylformamide inthe presence of methanesulphonyl chloride and lithiumchloride at 75 "C furnished l-chloro-2,3-dihydro-7-met hoxy-6-methyl-5,8-dioxo- 1 H-pyrrolo 1,2-aindole-9-carbaldehyde (29).Dehydration of (28) and dehydro-29chlorination of (29) under several sets of conditions gaveunsatisfactory results. The nitrile (7) was convertedinto methyl 2,3-dihydro-7-met hoxy-6-methyl- 1 H-pyr-rolo 1,2-aindole-9-carboxylate (8) in 65 yield byhydrolysis with potassium hydroxide in aqueousethylene glycol, followed by esterification with diazo-methane.Acetoxylation of (8) was carried out with1 mol. equiv. of lead tetra-acetate in acetic acid at roomtemperature, and the acetate (17), obtained in 71yield, was then hydrolysed to the alcohol (21) in 79yield with aqueous methanolic sodium hydrogencarbonate. Oxidation of the alcohol (21) with man-ganese dioxide gave me thy1 2,3-dihydro-7-me t hoxy-6-methyl-l-oxo-lH-pyrrolol,2-aindole-9-carboxylate (23)in 80 yield.Heating the acetate (17) in acetic acid furnishedmethyl 7-methoxy-6-methyl-3H-pyrrolo 1,2-aindole-9-carboxylate (26), whose spectral data were consistentwith those rep~rted.~ The olefinic compound (26) hasbeen transformed into the N-methoxycarbonylazirino-pyrrolol,2-aindole (3) by Matsui and his co-~orkers.~EXPERIMENTALM.p.s were taken with a Yanagimoto apparatus (MP-S2).1.r. spectra were measured with a Hitachi EPI-3 recordingspectrophotometer, n.m.r.spectra with a JEOL JNM-PMX60 spect)-ophotometer, and mass spectra with a HitachiRMU-7 spectrometer.6-Formy l- 2,3-dihydro- 7-methoxy - 1H-fiywoZo I , 2-ajindole-9-carbonitrile (9) .-A solution of the nitrile ( 5 ) (28 mg) and2,3-dichloro-5,6-dicyano- 1,4-benzoquinone (62 mg) inmethanol ( 5 ml) was stirred a t room temperature for 2 h togive a precipitate which was filtered off.The filtrate wasconcentrated and chromatographed on alumina (Woelm,grade 111). Elution with chloroform gave a solid whichwas recrystallised from chloroform to give the aldehyde (9)(21 mg, 71) asfirisms, m.p. 254-255" (Found: C, 70.05;H, 4.95; N, 11.65. C,,H,,N,O, requires C, 70.0; H, 5.05;N, 11.65), vmx. (CHCl,) 1664 (GO) and 2 210 cm-1(CN); 6 (CDCl,) 2.45-3.50 (4 H, m, 1- and 2-H,), 3.96(3 H, s, OMe), 4.20 (2 H, t, J 6 Hz, 3-H,), 7.02 (each 1 H,each s, 5- and 8-H respectively), and 10.42 (1 H, s, CHO);m/e 240 (M+).8-Bromo-2,3-dihydro- 5,7-dimethoxy- 6-methy Z- 1 H-pyrrolo- 1,2-aindoZe-9-carbonitrile (1 1) and 8-Bromo-2,3-dihydro-7-methoxy-6-methyZ-lH-pyr~oZo 1,2-aindoZe-9-carbonitrile (10).-A solution of the nitrile (5) (0.45 g) and N-bromo-succinimide (0.36 g) in methanol (300 ml) was stirred a troom temperature for 1 h, then evaporated.The residuewas chromatographed on silica gel (15 g). Elution withbenzene gave a solid, which was recrystallised from methanolto give (11) as needles (188 mg, 31), m.p. 119-121"(Found: C, 53.55; H, 4.45; N, 8.15. C,,H,,BrN,O,requires C, 53.75; H, 4.5; N, 8.35), vmx. (CHC1,) 2 210cm-l (CN); 6 (CDCl,) 2.42 (3 H, s, ArMe), 2.30-3.30 (4 H,m, 1- and 2-H,), 3.84 and 4.00 (each 3 H, each s, 2 x OMe),and 4.56 (2 H, t, J 6 Hz, 3-H,); m/e 336/334 (M+).Benzene-methanol (99 : 1 v/v) eluted a solid which was re-crystallised from chloroform to give (10) (173 mg, 29) asneedles, m.p.222-224" (Found: C, 54.85; H, 4.3; N, 9.15.C,,H,,BrN,O requires C, 55.1; H, 4.3; N, 9.15), vmK(CHCl,) 2 210 cm-l (CN); 6 (CDCl,) 2.34 (3 H, s, ArMe),2.50-3.30 (4 H, m, 1- and 2-H,), 3.80 (3 H, s, OMe), 4.0J.C.S. Perkin I(2 H, t, J 6 Hz, 3-H,), and 6.90 (1 H, s, 5-H); m/e 306/304Methyl 2,3-Dihydro- 7-methoxy- 6-methyl- 1 H-pyrroZo 1,2-a-indole-9-carboxylate (8).-A mixture of the nitrile (7) (2.26 g),potassium hydroxide (10 g), ethylene glycol (5 ml), andwater (5 ml) was stirred under reflux for 48 h, then acidifiedwith 10 hydrochloric acid and extracted with chloroform.The extract was evaporated, the residue was dissolved. inmethanol, and a solution of diazomethane in ether wasadded. The resulting mixture was set aside at roomtemperature for 5 h.Evaporation afforded a solid whichwas recrystallised from ether to give the ester (8) (1.68 g,65y0), m.p. 147-149' (Found: C, 69.5; H, 6.7; N, 5.1.C15H17N0, requires C, 69.5; H, 6.6; N, 5.4y0), vmx. (CHC1,)1 680 cm-l (GO); 6 (CDC1,) 2.34 (3 H, s, ArMe), 2.40-3.50(4 H, m, 1- and 2-H,), 3.86 and 3.90 (each 3 H, each s,2 x OMe), 4.00 (2 H, t, J 7 Hz, 3-H,), and 6.96 and 7.56(each 1 H, each s, 5- and 8-H); m/e 259 (Mf).l-Acetoxy-2,3-dihydr0-6,7-dimethoxy-lH-pyrroZo 1 , 2-a-indole-9-carbonitrile (13) .-A solution of the nitrile (4)(0.24 g) and lead tetra-acetate (0.66 g) in acetic acid (30mg) was stirred at room temperature under nitrogen for5 h, then evaporated under reduced pressure a t 40 'C.The residue was dissolved in water and extracted with-benzene.The organic layer was washed with aqueoussodium hydrogen carbonate solution and water, dried(Na,SO,), and evaporated to give a brown solid which wasrecrystallised from ethanol to afford (13) (0.23 g, 76) asneedles, m.p. 192-193" (Found: C, 63.8; H, 5.45; N, 9.4.C16H16N,0, requires C, 64.0; H, 5.35; N, 9.35), vmx.(CHCI,) 2 210 (CN) and 1 730 cm-l (GO) ; 6 (CDCI,) 2.14(3 H, s, Ac), 3.95 (6 H, s, 2 x OMe), 6.30 (1 H, dd, J 3 and7 Hz, 1-H), 6.80 (1 H, s, 5-H), and 7.14 (1 H, s, 8-H); mle300 (M+).1-A cetoxy-2,3-dihydro- 7-methoxy- 6-methyl- 1H-pyrrolo- 1,2-aindole-9-carbon~triZe (14) .-A solution of the nitrile(5) (0.45 g) and lead tetra-acetate (1.32 g) in acetic acid(40 ml) was stirred at room temperature under nitrogen for5 h.Work-up as above gave the acetate (14) (0.42 g, 74),m.p. 133-134" (from ether) (Found: C, 67.6; H, 5.7; N,9.85. C16H16N203 requires C, 67.6; H, 5.65; N, 9.85),vmx. (CHC1,) 2 210 (CN) and 1 730 cm-l (GO) ; 6 (CDC1,)2.10 (3 H, s, Ac), 2.30 (3 H, s, ArMe), 3.86 (3 H, s, OMe),6.26 (1 H, dd, J 3 and 7 Hz, 1-H), and 7.02 and 7.06 (each1 H, each s, 5- and 8-H, respectively) ; m/e 284 ( M f ) .l-Acetoxy-2,3-dihydro-6,7-dimethoxy- lH-Pyrrolo 1,2-a-indoze-9-curbaldehyde (15) .-A solution of the aldehyde (6)(0.44 g) and lead tetra-acetate (1.18 g) in acetic acid (30 ml)was stirred at room temperature under nitrogen for 15 h.Work-up as above gave (15) (0.36 g, 65) as needles, m.p.182-183' (from ethanol) (Found: C, 62.85; H, 5.6; N,5.0.C,,H17N0, requires C, 63.35; H, 5.65; N, 4.6),vDx. (CHCl,) 1730 (GO) and 1 640 cm-1 (CHO); 6 (CDCl,)2.06 (3 H, s, Ac), 3.89 (3 H, s, OMe), 3.92 (3 H, s, OMe),6.42 (1 H, dd, J 3 and 7 Hz, 1-H), 6.72 (1 H, s, 5-H), 7.75(1 H, s, 8-H), and 9.96 (1 H, s, CHO); m/e 303 ( M j ) . 1,2-aindole-9-carbaldehyde (16) .-A solution of thealdehyde (7) (0.23 g) and lead tetra-acetate (0.66 g) inacetic acid (20 ml) was stirred a t room temperature undernitrogen for 15 h. Work-up as above gave (16) (0.22 g,74) as needles, m.p. 169-170' (from ether-ethanol) (lit.,,170-172"), vmaK (CHC1,) 1730 (C=O) and 1640 cm-l(CHO); 6 (CDC1,) 2.10 (3 H, s, Ac), 2.34 (3 H, s, ArMe),3.92 (3 H, s, OMe), 6.48 (1 H, dd, J 3 and 7 Hz, 1-H), 7.06(M+).1-A cetoxy- 2 , 3-dihydro-7-methoxy- 6-methyl- 1H-PyrroZo-(1 H, s, 5-H), 7.72 (1 H, s, 8-H), and 9.96 (1 H, s, CHO);m/e 287 (M+).Methyl l-Acetoxy-2,3-dihydro-7-methoxy-6-rnethyl- 1H-pyr-rolol,2-aindole-9-carboxyZate (17) .-A solution of the ester(8) (0.7 g) and lead tetra-acetate (1.8 g) in acetic acid (60 ml)was stirred at room temperature for 15 h under nitrogen.Work-up as above gave (17) (0.61 g, 71) as prisms, m.p.136-138" (from ether-n-hexane) (Found: C, 64.15; H,5.95; N, 4.35.C1,Hl,N05 requires C, 64.35; H, 6.05;N, 4.4y0), vmx. (CHCI,) 1730 (C=O) and 1680 cm-1 (GO),6 (CDC1,) 2.06 (3 H, s, Ac), 2.34 (3 H, s, ArMe), 3.84 and3.92 (each 3 H, each s, 2 x OMe), 6.52 (1 H, dd, J 3 and7 Hz, 1-H), 7.02 (1 H, s, 5-H), and 7.56 (1 H, s, 8-H); mle317 (M+). 1,2-aindoZe-9-carbonitrile ( 18) .-A solution of the nitrile(4) (0.48 g) and lead tetra-acetate (2.65 g) in acetic acid(20 ml) was stirred at room temperature under nitrogen for48 h.The mixture was then heated at 100 "C for 4 h, andevaporated under reduced pressure, and the residue wasdissolved in water and extracted with benzene. Theextract was washed with aqueous sodium hydrogencarbonate solution and water, dried (Na,SO,), and evapor-ated to leave a syrup, which was chromatographed onalumina (Woelm, grade 111). Elution with benzene gave asolid, recrystallisation of which from ether afforded (18)(76 mg, 11) as needles, m.p. 163-164" (Found: C, 60.15;H, 5.25; N, 7.9. C,,Hl,N,06 requires C, 60.35; H, 5.05;N, 7.8y0), vmZ (CHCI,) 2 210 (CN) and 1730 cm-l (GO);6 (CDCI,) 2.13 (3 H, s, Ac), 2.42 (3 H, s, Ac), 3.86 (3 H, s,OMe), 3.94 (3 H, s, OMe), 6.26 (1 H, dd, J 3 and 7 Hz,1-H), and 7.02 (1 H, s, 5-H); m/e 358 (M+).1 -A cetoxy- 6-acetoxymethyl- 2,3-dihydro- 7-methoxy- 1 H-pyr-roZo 1,2-aindole-9-carbonitriZe (1 9) .-A solution of thenitrile (5) (0.45 g) and lead tetra-acetate (2.64 g) in aceticacid (20 ml) was stirred at 90 "C under nitrogen for 9 h,then evaporated.The residue was dissolved in water andextracted with benzene. The organic layer was washedwith aqueous sodium hydrogen carbonate solution andwater, dried (Na,SO,) , and evaporated. The residualreddish syrup was chromatographed on silica gel. Elutionwith benzene gave a solid, recrystallisation of which frommethanol afforded (19) (120 mg, 18) as brownish needles,m.p.158-160" (Found: C, 63.15; H, 5.45; N, 8.0.C,,H1,N,O5 requires C, 63.15; H, 5.3; N, 8.2), vmx.(CHCI,) 2 210 (CN) and 1 730 cm-l (GO); 6 (CDCI,) 2.10(6 H, s, 2 x Ac), 3.86 (3 H, s, OMe), 5.20 (2 H, s, ArCH,*O),6.24 (1 H, dd, J 3 and 7 Hz, 1-H), 7.02 and 7.26 (each 1 H,each s, 5- and 8-H, respectively) ; m/e 342 (M+).2,3-Dihydro- l-hydroxy-7-methoxy-6-methyl- 1H-pyrrolo- 1,2-aindole-9-carbaldehyde (20) .-A solution of the aldehyde(16) (0.574 g) in methanolic potassium hydroxide (40 ml)was refluxed for 30 min, then evaporated, and the residuewas extracted with benzene. The extract was washed withwater, dried (Na,SO,), and evaporated to leave a solid,which afforded (20) (0.421 g, 86) as needZes, m.p.154-155" (from ethanol) (Found: C, 68.2; H, 6.0; N, 5.7.Cl,H15N0, requires C, 68.55; H, 6.15; N, 5.7y0), v-(CHCl,) 1630 cm-l (GO); 6 (CDCl,) 2.22 (3 H, s, ArMe),3.80 (3 H, s, OMe), 5.36 (1 H, t, J 6 Hz, 1-H), 6.66 (1 H, s,5-H), 7.28 (1 H, s, 8-H), 9.76 (1 euro;3, s, CHO); m/e 245 (M').Methyl 2,3-Dihydro- l-hydroxy-7-methoxy-6-methyZ- 1H-pyr-rolo 1,2-aindole-9-carboxyZute (21) .-A mixture of the ester(17) (160 mg) , saturated sodium hydrogen carbonatesolution (12 ml), water (20 ml), and methanol (60 ml) was1,8-Diacetoxy-2,3-dihydr0-6,7-dimethoxy- 1H-pyrrolo1977stirred at room temperature for 24 h, and then concen-trated under reduced pressure. The residue was extractedwith chloroform.The extract was washed with water,dried (Na,SO,), and evaporated to leave a syrup, whichwas chromatographed on silica gel. Elution with benzenegave a solid, recrystallisation of which from ether afforded(21) (110 mg, 79) as prisms, m.p. 121-123" (Found: C,65.5; H, 6.2; N, 5.1. C15H,,N0, requires C, 65.45; H,6.2; N, 5.1), vmx. (CHC1,) 1660 cm-l (GO); 6 (CDCl,)2.28 (3 H, s, ArMe), 3.86 and 3.92 (each 3 H, each s, 2 xOMe), 5.54 (1 H, t, J 6 Hz, 1-H), and 7.00 and 7.38 (each1 H, s, 5- and 8-H); m/e 275 (M+).2,3-Dihydro- l-hydroxy- 7-methoxy-6-methyl-5,8-dioxo- 1H-pyrrolo 1,2-aindole-9-carbaldehyde (28) .-A mixture of thequinone (27) 3 (90 mg), saturated sodium hydrogen carbonatesolution (6 ml), water (10 ml), and methanol (30 ml) wasstirred a t room temperature for 1 h, then concentratedunder reduced pressure a t 15 "C.The residue was ex-tracted with chloroform and the organic layer was washedwith water, dried (Na,SO,), and evaporated to leave asolid, recrystallisation of which from ethanol afforded (28)(74 mg, 95) as orange needles, m.p. 179-181" (Found: C,61.45; H, 5.05; N, 5.25. C,,H,,NO, requires C, 61.1; H,4.75; N, 5.1y0), vmx. (CHCl,) 1 660, 1 650, and 1 636 cm-1(GO); 6 (CDCl,) 1.96 (3 H, s, ArMe), 4.02 (3 H, s, OMe),5.40 ( 1 H, t, J 6 Hz, 1-H), and 1C.20 (1 H, s, CHO); m/e275 (M').2,3-Dihydro- 7-methoxy-6-methyl- l-oxo- lH-PyrroEo 1,2-a-indole-9-carbaldehyde (22) .-To a solution of the aldehyde(20) (0.25 g) in inethylene chloride (10 ml) was addedactivated manganese dioxide (2 g).The mixture wasstirred a t room temperature for 2 h, then filtered throughCelite, and the Celite and inorganic material were washedwith methylene chloride. The combined filtrate andwashings were concentrated to leave a solid, which wasrecrystallised from chloroform to give (22) as pale yellowneedles (0.18 g, 74y0), m.p. 248-249' (Found: C, 68.7;H, 5.45; N, 5.85. C14H,,N0, requires C, 69.1; H, 5.4;N, 5.75), vmax. (CHCl,) 1 710 (GO) and 1 655 cm-l (GO);6 (CDC1,) 2.34 ( 3 H, s, ArMe), 3.22 (2 H, t, J 6 Hz, 2-H,),3.92 (3 H, s, OMe), 4.22 (2 H, t, J 6 Hz, 3-H,), 7.34 and7.76 (each 1 H, each s, 5- and 8-H, respectively), and10.34 (1 H, s, CHO) ; m/e 243 (M+).Methyl 2,3-Dihydro- 7-methoxy-6-methyl- l-oxo- 1 H-pyrrolo- 1,2-aindoZe-9-carboxyZute (23) .-A mixture of the ester(21) (20 mg), activated manganese dioxide (200 mg), andmethylene chloride (3 ml) was stirred at room temperatureunder nitrogen for 7 h.Work-up as above gave (23)(16 mg, 80) as pale yellow prisms, m.p. 213-215' (frommethanol) (Found: C, 65.9; H, 5.8; N, 5.5. C15H15N0,requires C, 65.9; H, 5.55; N, 5.1y0), vmx. (CHC1,) 1720(GO) and 1 700 cm-l (GO) ; 6 (CDCl,) 2.30 (3 H, s, ArMe),3.16 (2 H, t, J 6 Hz, 2-H,), 3.86 and 3.92 (each 3 H, each s,2 x OMe), 4.30 (2 H, t, J 6 Hz, 3-H,), 7.10 and 7.54 (each1 H, each s, 8- and 5-H) ; m/e 273 (M+).1 -ChZoro- 2,3-dihydro- 7-methoxy- 6-methyl- 5,8-dioxo- 1H-pyrrolo 1,2-aindoZe-9-carbaldehyde (29) .-A mixture of thealdehyde (28) ( 10 mg), methanesulphonyl chloride ( 1 ml) ,and lithium chloride ( 1 g) in dry dimethylformamide (2 ml)was stirred a t 75 "C under nitrogen for 45 min.Themixture was diluted with water, basified with solid sodiumhydrogen carbonate, and extracted with chloroform. Theorganic layer was washed with water, dried (Na,SO,), andevaporated to leave an oil, which was chromatographed onsilica gel. Elution with chloroform gave an orange solid,v,, (CHCl,) 1 675, 1 660, and 1 640 cm-l (GO); 6 (CDC1,)1.94 (3 H, s, ArMe), 4.00 (3 H, s, OMe), 4.96 (1 H, t, J 6 Hz,1-H), and 10.34 (1 H, s, CHO) ; m/e 295 (M+), which wasunstable at room temperature.6,7-Dimethoxy-3H-~yrrolo 1,2-aindole-9-carbonitrile (24).-A solution of the nitrile (13) (60 mg) in acetic acid (5 ml)was heated at 90-100 "C for 6 h, then evaporated underreduced pressure to leave a solid, which was chromato-graphed on silica gel.Elution with chloroform eluate gavea solid, recrystallisation of which from methanol gave (13)(23 mg, 48) as needles, m.p. 171-172" (Found: C, 69.6;H, 5.0; N, 11.65. Cl,H1,N,O, requires C, 70.0; H, 5.0;N, 11.65y0), vmax. (CHC1,) 2 210 cm-l (CN); 6 (CDC1,)3.92 (6 H, s, 2 x OMe), 4.58br (2 H, s, 3-H,), 6.48br (3 H,s, 1-, 2-, and 5-H), and 7.06 (1 H, s, 8-H); m/e 240 (M+).7-Methoxy-6-methyl-3H-pyrrolo 1,2-aindole-9-carbonitrile(25).-A solution of the nitrile (14) (60 mg) in acetic acid(3 ml) was heated at 105-1 10 "C under a stream of nitrogenfor 5 h, then evaporated under reduced pressure. Theresidue was chromatographed on silica gel. Benzene-chloroform (1 : 1 v/v) eluted a syrup which was purified bythick-layer chromatography on silica gel (chloroform).Recrystallisation from methanol gave needles (25 mg, 53),m.p. 142-143" (Found: C, 74.95; H, 5.4; N, 12.75.Cl,Hl,N,O requires C, 75.0; H, 5.4; N, 12.5), v,,(CHCl,) 2 210 cm-l (CN); 6 (CDCl,) 2.30 (3 H, s, ArMe),3.84 (3 H, s, OMe), 4.54br (2 H, s, 3-H,), and 6.70-7.00(4 H, m, 2 x ArH and 2 x olefinic H); m/e 224 (M+).'I-Methoxy-6-methy1-3H-pyrrolo 1 , 2-alindole-9-carboxylate (26).-A solution of the ester (17) (32 mg) inacetic acid (5 ml) was heated a t 105-110 "C for 3 h, thenevaporated under reduced pressure. The residual syrupwas chromatographed on silica gel. Elution with benzene-chloroform (1 : 1 v/v) gave a syrup which was purified bythick-layer chromatography on silica gel (chloroform) togive a solid (6 mg, 23). This was recrystallised frommethanol to give prisms, m.p. 153-155" (lit.,, 151--155O),vWx. (CHC1,) 1680 cm-l (GO); 6 (CDC1,) 2.26 (3 H, s,ArMe), 3.82 and 3.89 (each 3 H, each s, 2 x OMe), 4.45s, 5-H), 7.02 (1 H, m, 2-H), and 7.48 (1 H, s, 8-H); m/e257 (M').Methyl(3 H, t, J 2 Hz, 3-H,), 6.52 (1 H, d, J 6 Hz, 1-H), 6.88 (1 H,We thank Dr. M. Koizumi, Mr. K. Kawamura, Mrs. C.Koyanagi, Miss K. Mushiake, Mrs. R. Kobayashi, Miss R.Suenaga, Miss E. Nagaoka, and Miss M. Tanno for micro-analyses and spectral measurements.6/1226 Received, 24th June, 1976