Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(O)(=O)C(O)=O.[C:7]([C:10]1([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[S:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][CH2:11]1)(=[O:9])[CH3:8].C(=O)([O-])[O-].[K+].[K+].[N:36]#CBr>C(Cl)(Cl)Cl>[C:7]([C:10]1([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[S:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:15][CH2:14][N:13]([C:16]#[N:36])[CH2:12][CH2:11]1)(=[O:9])[CH3:8]
Reactant: CC(=O)C1(c2ccccc2Sc2ccccc2)CCN(C)CC1
Reactant: N#CBr
Agent: O=C(O)C(=O)O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClC(Cl)Cl
Product: CC(=O)C1(c2ccccc2Sc2ccccc2)CCN(C#N)CC1

Procedure:
A solution of 6.8 g of 4-acetyl-1-methyl-4-(2-phenylthiophenyl)piperidine oxalate, Example 6, in 40 ml of chloroform is added dropwise to a rapidly stirring mixture of 14.7 g of potassium carbonate and 3.7 g of cyanogen bromide in 48.5 ml of chloroform. After total addition, the reaction mixture is successively stirred at reflux for 16 hours, filtered, washed five times with 100 ml portions of water, washed with one 50 ml portion of a saturated sodium chloride solution and dried. The resulting product is purified by chromatography (silica gel column, ether eluant) to provide 4-acetyl-1-cyano-4-(2-phenylthiophenyl)piperidine.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:13]=C(C2C=CC=CC=2)C2C=CC=CC=2)[CH:5]=[C:6]2[C:10]=1[C:9]([CH3:12])([CH3:11])[CH2:8][CH2:7]2.Cl.[OH-].[Na+]>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([NH2:13])[CH:5]=[C:6]2[C:10]=1[C:9]([CH3:11])([CH3:12])[CH2:8][CH2:7]2
Reactant: CC1(C)CCc2cc(N=C(c3ccccc3)c3ccccc3)cc(F)c21
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CC1(C)CCc2cc(N)cc(F)c21
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of the crude N-(7-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)-1,1-diphenylmethanimine in THF (30 mL) was added LM hydrochloric acid (29 mL, 29.17 mmol) at room temperature, and the mixture was stirred at room temperature for 30 min. The pH of the reaction mixture was adjusted to >7 with sodium hydroxide, and the mixture was extracted with ethyl acetate (×2). The organic layer was washed with 10% brine, dried over sodium sulfate, and concentrated under reduced pressure to give the crude 7-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-amine as an orange oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[N:15]1[C:23]2[C:18](=[CH:19][CH:20]=[C:21]([NH2:24])[CH:22]=2)[CH2:17][CH2:16]1.N1C=CC=CC=1.[C:31](Cl)(=[O:33])[CH3:32]>C(Cl)(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[N:15]1[C:23]2[C:18](=[CH:19][CH:20]=[C:21]([NH:24][C:31](=[O:33])[CH3:32])[CH:22]=2)[CH2:17][CH2:16]1
Reactant: CC(=O)Cl
Reactant: COc1cc2ncnc(N3CCc4ccc(N)cc43)c2cc1OC
Solvent: c1ccncc1
Solvent: ClC(Cl)Cl
Product: COc1cc2ncnc(N3CCc4ccc(NC(C)=O)cc43)c2cc1OC
Yield: 68.8 %

Procedure:
To 1-(6,7-dimethoxy-quinazolin-4-yl)-2,3-dihydro-1H-indol-6-ylamine (99 mg, 0.307 mmol; from Example 30) and pyridine (32 μL, 0.620 mmol) in CHCl3 (5 mL) was added acetyl chloride (33 μL, 0.455 mmol). The mixture was refluxed 2 hours, diluted with CHCl3 (15 mL), and the organic solution was washed with saturated aqueous NaHCO3, dried over Na2SO4(s), filtered and concentrated in vacuo. Flash chromatography on silica (5% MeOH/CHCl3) afforded 77 mg of product. (M.P. 223°-229° C. (dec); GC-MS: 364 (M+); anal. RP18-HPLC RT: 3.42 min.).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][C:9]=2[CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[N:28]([CH:29]4[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]4)[N:27]=[C:26](/[CH:35]=[CH:36]/[C:37]([O:39]C)=[O:38])[CH:25]=3)=[CH:20][CH:19]=2)=[CH:4][CH:3]=1.[Li+].[OH-]>CO.C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][C:9]=2[CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[N:28]([CH:29]4[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]4)[N:27]=[C:26](/[CH:35]=[CH:36]/[C:37]([OH:39])=[O:38])[CH:25]=3)=[CH:20][CH:19]=2)=[CH:4][CH:3]=1
Reactant: COC(=O)/C=C/c1cc(-c2ccc(OCc3cc(OC)ccc3-c3ccc(Cl)cc3)cc2)n(C2CCCCC2)n1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: COc1ccc(-c2ccc(Cl)cc2)c(COc2ccc(-c3cc(/C=C/C(=O)O)nn3C3CCCCC3)cc2)c1

Procedure:
Methyl ester 3.2 (40 mg) and 1N LiOH (1 ml) in 3 ml MeOH/THF (1:2) was stirred at rt 18 h before being concentrated and partitioned between EtOAc and H2O. The aqueous layer was acidified with 1N HCl and extracted with EtOAc (3×). The organic extracts were washed with H2O, brine, and dried (Na2SO4). Concentration gave 3.3, 39 mg (100%). HRMS (ESI) calc'd for C32H32ClN2O4 542.1972; found 543.2050 (MH+); 1H NMR (300 MHz, CDCl3) δ 7.83 (d, J=15.8, 1H), 7.39–7.23 (m, 7H), 7.18 (d, J=2.6, 1H), 6.99–6.94 (m, 3H), 6.45 (s, 1H), 6.38 (d, J=6.1, 1H), 4.94 (s, 2H), 4.13–4.01 (m, 1H), 3.88 (s, 3H), 2.04–1.83 (m, 6H), 1.32–1.21 (m, 4H).
Reaction SMILES: Br[CH2:2][CH2:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][C:12]=1[Cl:13])[NH:9][C:8](=[O:14])[CH2:7]2.[S:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[C:17]([N:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)=[N:16]1>O>[CH:22]1[CH:21]=[CH:20][C:19]2[S:15][N:16]=[C:17]([N:24]3[CH2:25][CH2:26][N:27]([CH2:2][CH2:3][C:4]4[CH:5]=[C:6]5[CH2:7][C:8](=[O:14])[NH:9][C:10]5=[CH:11][C:12]=4[Cl:13])[CH2:28][CH2:29]3)[C:18]=2[CH:23]=1
Reactant: c1ccc2c(N3CCNCC3)nsc2c1
Reactant: O=C1Cc2cc(CCBr)c(Cl)cc2N1
Solvent: O
Product: O=C1Cc2cc(CCN3CCN(c4nsc5ccccc45)CC3)c(Cl)cc2N1
Temperature: 99 °C
Reaction time: 1.17 h

Procedure:
To de-ionized water (1.5 Lit), was added 5-(2-bromoethyl)-6-chloro-oxindole (75 g) and 1-(1,2-benzisothiazol-3-yl)piperazine (132 g) at 30-35° C. The mixture was slowly heated under stirring to 98-100° C. over 60-80 minutes. The resultant mass was stirred for 4-5 hours at 98-100° C. After completion of reaction as monitored by HPLC, the suspended solid material was filtered at 98-100° C. The wet cake so obtained was suspended in de-ionized water (1.5 Lit) and heated to 90-95° C. and further maintained at this temperature for 30 minutes. The solid suspension was filtered at 90-95° C. The wet cake was further added to isopropyl alcohol (1.5 Lit) and the resultant mass was heated to reflux and maintained at reflux for 1 hour. The mass was further cooled to 30-35° C. and stirred for 2 hours at 30-35° C. The solids were filtered and washed with isopropyl alcohol (75 ml) and dried under vacuum at 50-55° C. for 7-8 hours till moisture content was not more than 1.0% w/w.
Reaction SMILES: [Br-].[CH2:2]([O:9][CH2:10][CH2:11][CH2:12][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[NH2:42][C:43]1[N:48]=[C:47]([CH:49]([CH3:51])[CH3:50])[C:46]([C:52]([O:54][CH3:55])=[O:53])=[C:45]([C:56]2[CH:61]=[CH:60][C:59]([F:62])=[CH:58][CH:57]=2)[C:44]=1[CH:63]=O.[NH4+].[Cl-]>O1CCCC1.C(OCC)(=O)C>[NH2:42][C:43]1[C:44](/[CH:63]=[CH:12]/[CH2:11][CH2:10][O:9][CH2:2][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)=[C:45]([C:56]2[CH:57]=[CH:58][C:59]([F:62])=[CH:60][CH:61]=2)[C:46]([C:52]([O:54][CH3:55])=[O:53])=[C:47]([CH:49]([CH3:51])[CH3:50])[N:48]=1
Reactant: COC(=O)c1c(C(C)C)nc(N)c(C=O)c1-c1ccc(F)cc1
Reactant: c1ccc(COCCC[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Br-]
Agent: [Cl-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COC(=O)c1c(C(C)C)nc(N)c(/C=C/CCOCc2ccccc2)c1-c1ccc(F)cc1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 81.7 %

Procedure:
To a suspension of (3-benzyloxypropyl)triphenyl-phosphonium bromide (8.55 g, 17.4 mmol) in tetrahydrofuran (15 mL) was added dropwise sodium bis(trimethylsilyl)amide (34.8 mL, 1.0 M in tetrahydrofuran) under nitrogen at −78° C. The reaction was stirred at −78° C. for 30 min, allowed to warm to room temperature and stirred for another 30 min. The mixture was then cooled to −78° C. and a solution of methyl 6-amino-4-(4-fluorophenyl)-5-formyl-2-(1-methylethyl)-3-pyridinecarboxylate (5.0 g, 15.8 mmol) in tetrahydrofuran (10 mL) was added dropwise over 45 min. The resulting mixture was stirred at −78° C. for 30 min, allowed to warm to room temperature and stirred for 2 h. The resulting mixture was then poured into a mixture of ice, ethyl acetate, saturated aqueous NH4Cl and was extracted with ethyl acetate. The combined organic layers were washed with brine and evaporated. The residue was equally divided and portion was purified by a silica gel chromatography (120 g column), using 0% to 45% of ethyl acetate in hexanes. The collected fractions were concentrated to provide methyl (E)-6-amino-5-(4-(phenylmethoxy)but-1-enyl)-4-(4-fluorophenyl)-2-(1-methylethyl)nicotinate as a light orange oil (5.79 g, 82%): LCMS (ESI, pos. ion spectrum) m/z 449 (M+H); HPLC (method 3) tR=3.2 min.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[Li]CCCC.[CH2:15]([O:17][C:18]1[CH:19]=[C:20]([O:35][CH:36]([CH3:38])[CH3:37])[C:21]([F:34])=[C:22]([CH:33]=1)/[CH:23]=[N:24]/[C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][CH:26]=1)[CH3:16]>C1COCC1>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[N:24]([CH2:23][C:22]1[CH:33]=[C:18]([O:17][CH2:15][CH3:16])[CH:19]=[C:20]([O:35][CH:36]([CH3:38])[CH3:37])[C:21]=1[F:34])[C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][CH:26]=1
Reactant: c1ccc2scnc2c1
Reactant: CCOc1cc(/C=N/c2ccc(C#N)cc2)c(F)c(OC(C)C)c1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCOc1cc(CN(c2ccc(C#N)cc2)c2nc3ccccc3s2)c(F)c(OC(C)C)c1
Temperature: -78 °C
Reaction time: 0.75 h
Yield: 42.6 %

Procedure:
To a solution of benzothiazole (61.9 mg, 0.458 mmol) in 2 mL THF at −78° C. was added 1.6 M solution of BuLi in THF (315 μL, 0.504 mmol). The mixture was stirred at −78° C. for 45 min, then a solution of Intermediate 7.3 (149 mg, 0.458 mmol) in 0.5 mL THF was added dropwise. The mixture was stirred and allowed to warm to rt overnight, then was quenched with sat. NH4Cl. The mixture was diluted with EtOAc, washed with H2O and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 50% EtOAc/hexanes gradient) to afford 90 mg of Intermediate 7.4 as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:19])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:7][CH:6]=1.[C:20](=O)([O-])[O-].[K+].[K+].C=O>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:19])[C:4]([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[CH:7][CH:6]=1)=[CH2:20]
Reactant: O=C([O-])[O-]
Reactant: COC(=O)Cc1ccc(OCc2ccccc2)cc1
Agent: C=O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [I-]
Solvent: Cc1ccccc1
Product: C=C(C(=O)OC)c1ccc(OCc2ccccc2)cc1
Temperature: 27.5 °C

Procedure:
(4-benzyloxy-phenyl)-acetic acid methyl ester (10 g; 0.04 mol)) was charged to toluene (100 ml). Further potassium carbonate (13.47 g; 0.09 mol), paraformaldehyde (2.9 g, 0.097 mol) and tetrabutyl ammonium iodide (0.72 g) were charged and the reaction mixture thus obtained was refluxed for 5.5-6 hours. The reaction mass was cooled to 25-30° C. and filtered. The filtrate contains 2-(4-benzyloxy-phenyl)-acrylic acid methyl ester.
Reaction SMILES: C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.Br[C:15]1[CH:16]=[CH:17][C:18]2[N:23]([CH:24]3[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25]3)[CH2:22][CH2:21][S:20][C:19]=2[CH:36]=1.[Li+].C[Si]([N-:42][Si](C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:42][C:15]1[CH:16]=[CH:17][C:18]2[N:23]([CH:24]3[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25]3)[CH2:22][CH2:21][S:20][C:19]=2[CH:36]=1
Reactant: CC(C)(C)OC(=O)N1CCC(N2CCSc3cc(Br)ccc32)C1
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Pd]
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(N2CCSc3cc(N)ccc32)C1
Temperature: 100 °C
Reaction time: 0.17 h
Yield: 83 %

Procedure:
Tris(dibenzylideneacetone)dipalladium(0) (0.056 g, 0.062 mmol) in THF (3 mL) was treated with tri-tert-butylphosphine 10% wt in hexanes (0.748 mL, 0.247 mmol) and was stirred vigorously under argon atmosphere for 10 minutes. tert-Butyl 3-(7-bromo-2H-benzo[b][1,4]thiazin-4(3H)-yl)pyrrolidine-1-carboxylate (0.49 g, 1.233 mmol) in THF (9 mL) and IM LiHMDS in THF (3.70 mL, 3.70 mmol) were added to the mixture. The reaction was sealed, placed in a preheated oil bath, and refluxed at 100° C. The solution was cooled to room temperature, treated with 1M TBAF in THF (8 mL), and was stirred for 40 minutes. The mixture was concentrated and treated with 1N NaOH (50 mL). The mixture was transferred to a separatory funnel, diluted with water (50 mL), and extracted with EtOAc (2×50 mL). The organic phase was washed with brine (50 mL) and dried (Na2SO4). The crude material was subject to flash chromatography on silica gel (25-70% EtOAc/hexanes). The collected fractions were concentrated to give a clear brown oil (0.34 g, 83%). 1H NMR (CDCl3) δ 6.64 (d, J=8.7 Hz, 1H), 6.48 (s, 1H), 6.39 (brs, 1H), 4.08-4.02 (m, 1H), 3.70-3.07 (m, 6H), 3.09-3.07 (m, 2H), 2.08-1.92 (m, 2H), 1.46 (s, 9H); ESI-MS (m/z, %): 338, 336 (MH+, 40), 282, 280 (100).
Reaction SMILES: [CH2:1]([C:3]1[C:7]([N:8]=O)=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[NH:5][N:4]=1)[CH3:2]>C(O)C.[Pd]>[NH2:8][C:7]1[C:3]([CH2:1][CH3:2])=[N:4][NH:5][C:6]=1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: CCc1n[nH]c(-c2ccccc2)c1N=O
Agent: [Pd]
Solvent: CCO
Product: CCc1n[nH]c(-c2ccccc2)c1N
Reaction time: 16 h

Procedure:
A solution of 6.3 g of 3-ethyl-4-nitroso-5-phenyl-1H-pyrazole in 220 mL of ethanol was treated with 2.0 g of 10% palladium/carbon catalyst and hydrogenated at RT and 50 psi for 16 h. The reaction mixture was filtered through celite and washed well with ethanol. The filtrate was concentrated to give the title compound as a brown oil.
Reaction SMILES: C([O:3][C:4](=O)[CH2:5][N:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][CH3:13])[C:7]1=[O:14])C.O.[NH2:17][NH2:18]>C(O)C>[CH3:13][O:12][C:8]1[C:7](=[O:14])[N:6]([CH2:5][C:4]([NH:17][NH2:18])=[O:3])[CH:11]=[CH:10][CH:9]=1
Reactant: NN
Reactant: CCOC(=O)Cn1cccc(OC)c1=O
Solvent: O
Solvent: CCO
Product: COc1cccn(CC(=O)NN)c1=O
Yield: 83 %

Procedure:
As described for example 112a, (3-methoxy-2-oxo-2H-pyridin-1-yl)-acetic acid ethyl ester in ethanol was reacted with hydrazine hydrate (1.2 equivalents) at rt for 16 h. The mixture was concentrated and crystallized from ethanol/diisopropylether and the compound was obtained as a white solid (yield: 83%). MS: m/e=220.1 [M+Na]+.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[N:7][N:8]3[C:15](=[O:16])[C:14]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:13][C:12]([C:23]([N:25]([CH3:27])[CH3:26])=[O:24])=[C:9]32)=[CH:4][CH:3]=1.Cl.C(O)C>CO>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][NH:7][N:8]3[C:15](=[O:16])[C:14]([C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)=[CH:13][C:12]([C:23]([N:25]([CH3:27])[CH3:26])=[O:24])=[C:9]32)=[CH:4][CH:3]=1
Reactant: CN(C)C(=O)c1cc(-c2ccccc2)c(=O)n2ncc3ccc(Cl)cc3c12
Agent: Cl
Solvent: CCO
Solvent: CO
Product: CN(C)C(=O)c1cc(-c2ccccc2)c(=O)n2c1-c1cc(Cl)ccc1CN2

Procedure:
from 10-chloro-N,N-dimethyl-4-oxo-3-phenyl-4H-pyrido[2,1-a]phthalazine-1-carboxamide in methanol/glacial acetic acid (10:1), but without the addition of saturated methanolic hydrochloric acid, there is obtained 10-chloro-6,7-dihydro-N,N-dimethyl-4-oxo-3-phenyl-4H-pyrido[2,1-a]phthalazine-1-carboxamide of m.p. 250°-252° (ethanol);
Reaction SMILES: [C:1]([C:3](=[CH:11]N(C)C)[C:4]([C:6]1[S:7][CH:8]=[CH:9][CH:10]=1)=O)#[N:2].[N+]([O-])([O-])=O.[N+:19]([C:22]1[CH:23]=[C:24]([NH:28][C:29]([NH2:31])=[NH2+:30])[CH:25]=[CH:26][CH:27]=1)([O-:21])=[O:20].[OH-].[Na+]>>[C:1]([C:3]1[C:4]([C:6]2[S:7][CH:8]=[CH:9][CH:10]=2)=[N:30][C:29]([NH:28][C:24]2[CH:25]=[CH:26][CH:27]=[C:22]([N+:19]([O-:21])=[O:20])[CH:23]=2)=[N:31][CH:11]=1)#[N:2]
Reactant: NC(=[NH2+])Nc1cccc([N+](=O)[O-])c1
Reactant: CN(C)C=C(C#N)C(=O)c1cccs1
Agent: O=[N+]([O-])[O-]
Agent: [Na+]
Agent: [OH-]
Product: N#Cc1cnc(Nc2cccc([N+](=O)[O-])c2)nc1-c1cccs1

Procedure:
5-Cyano-N-3-nitrophenyl-4-thien-2-ylpyrimidine-2-amine was prepared from 2-cyano-3-dimethylamino-1-thien-2-ylpropen-1-one (3.20 g, 15.51 mmol), 3-nitrophenylguanidinium nitrate (3.74 g, 15.53 mmol) and sodium hydroxide (652 mg, 7.82 mmol) to give the desired material (841 mg) as an off-white solid, m.p.275-277°. δH (d6 DMSO) 10.87 (1H, bs), 8.98 (1H, s), 8.90 (1H, bs), 8.31-8.29 (1H, m), 8.09-8.05 (2H, m), 7.91 (1H, dd, J 7.7,2.0 Hz), 7.64 (1H, t ,J 8.1 Hz) and 7.37-7.35 (1H, m).
Reaction SMILES: [CH2:1]1[C:11]2[N:10]3[C:12]4[CH:21]=[CH:20][N:19]=[CH:18][C:13]=4[C:14]4[CH2:15][CH2:16][CH:17]=[C:8]([C:9]=43)[CH:7]=[CH:6][C:5]=2[CH2:4][CH2:3][CH2:2]1.ClCCl.[CH:25]1([C:28](Cl)=[O:29])[CH2:27][CH2:26]1>C(N(CC)CC)C>[CH2:1]1[C:11]2[N:10]3[C:12]4[CH:21]=[CH:20][N:19]=[CH:18][C:13]=4[C:14]4[CH2:15][CH2:16][CH:17]=[C:8]([C:9]=43)[CH:7]=[CH:6][C:5]=2[CH2:4][CH:3]([C:28]([CH:25]2[CH2:27][CH2:26]2)=[O:29])[CH2:2]1
Reactant: O=C(Cl)C1CC1
Reactant: C1=CC2=C(CCCC2)n2c3c(c4cnccc42)CCC=C13
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(C1CC1)C1CCC2=C(C=CC3=CCCc4c3n2c2ccncc42)C1
Reaction time: 8 h

Procedure:
To a solution of 16.4 g. of the product of Example 1 in 500 ml. of dichloromethane, 7.3 g. of cyclopropanecarbonyl chloride is added, followed by dropwise addition of 10 ml. of triethylamine. A mildly exothermic reaction takes place, after which stirring of the mixture is continued at room temperature overnight. The mixture is then washed with 1N hydrochloric acid and water, and dried over anhydrous sodium carbonate. On evaporation to dryness, crude cyclopropyl 1,2,3,4,8,9-hexahydropyrido[4',3':2,3]indolo[1,7-ab][1]benzazepin-3-yl ketone is obtained as a glassy product, m.p. 149°-152° on recrystallization from ethanol. A solution of 8.6 g. of this material in 120 ml. of tetrahydrofuran is added dropwise to a suspension of 2.3 g. of lithium aluminum hydride in 180 ml. of tetrahydrofuran. On completion of the addition, the mixture is first refluxed for 4 hours, then allowed to stir at room temperature overnight and finally decomposed in the usual manner. After filtering off the inorganic salts, the filtrate is dried over anhydrous sodium carbonate, evaporated in vacuo; the residue is dissolved in a 1:1 mixture of ethyl acetate-benzene and chromatographed on a 14 × 2.2 cm. column of basic alumina, activity I. The eluate is taken down to dryness; the residual oil dissolved in absolute alcohol, saturated with ethanolic hydrogen chloride, and once again evaporated to dryness. Upon crystallization of the residue from acetone, 3-(cyclopropylmethyl)-1,2,3,4,8,9-hexahydropyrido[4',3':2,3]indolo[1,7-ab][1]benzazepine hydrochloride, m.p. 267°, is obtained.
Reaction SMILES: [BH4-].[Na+].[C:3]1([CH:13]([OH:22])[C:14]2[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=2[NH2:21])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=1.[Si:23]([O:40][CH2:41][C:42]([CH3:46])([CH3:45])[CH:43]=O)([C:36]([CH3:39])([CH3:38])[CH3:37])([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.O>C(O)(=O)C>[C:3]1([CH:13]([OH:22])[C:14]2[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=2[NH:21][CH2:43][C:42]([CH3:46])([CH3:45])[CH2:41][O:40][Si:23]([C:36]([CH3:39])([CH3:38])[CH3:37])([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=1
Reactant: CC(C)(C=O)CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Reactant: Nc1ccc(Cl)cc1C(O)c1cccc2ccccc12
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: CC(C)(CNc1ccc(Cl)cc1C(O)c1cccc2ccccc12)CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 57.4 %

Procedure:
Sodium borohydride (1.73 g, 45.8 mmol) was added portionwise to a solution of α-(1-naphthyl)-2-amino-5-chlorobenzyl alcohol (9.76 g, 34.4 mmol) and 3-tert-butyldiphenylsilyloxy-2,2-dimethylpropanal (12.89 g, 37.9 mmol) in acetic acid (105 ml) at 0° C. The reaction mixture was allowed to warm to room temperature, and stirring was continued for 45 min. Hydrolysis with water was followed by repeated extraction of the mixture with ethyl acetate. The combined organic layers were washed with 1 N sodium hydroxide and dried with MgSO4. The filtrate was concentrated under reduced pressure, and the residue was purified by flash chromatography (hexane/ethyl acetate 9:1) to give the title compound (12.01 g, 57%) as a colorless oil.
Reaction SMILES: C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][CH:13]1[C:21]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22].C(N(CC)CC)C.[C:38]([O:42][C:43]([NH:45][C@H:46]([C:48](O)=[O:49])[CH3:47])=[O:44])([CH3:41])([CH3:40])[CH3:39]>C(OCC)(=O)C>[C:38]([O:42][C:43]([NH:45][C@@H:46]([CH3:47])[C:48]([N:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][C@H:13]1[C:21]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22])=[O:49])=[O:44])([CH3:41])([CH3:40])[CH3:39]
Reactant: C[C@H](NC(=O)OC(C)(C)C)C(=O)O
Reactant: O=C(OCc1ccccc1)C1Cc2ccccc2N1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: C[C@H](NC(=O)OC(C)(C)C)C(=O)N1c2ccccc2C[C@H]1C(=O)OCc1ccccc1
Temperature: 30 °C

Procedure:
200 g of benzyl 2,3-dihydro-1H-indole-2-carboxylate para-toluenesulphonate, 66 ml of triethylamine and 1 litre of ethyl acetate are introduced into a stirred reactor, followed, after stirring for 10 minutes at ambient temperature, by 89 g of N-[tert-butyloxycarbonyl]-(S)-alanine and 151 g of O-(benzotriazol-1-yl)-1,1,3,3-bis(tetramethylene)uronium tetrafluoroborate. The heterogeneous mixture is then heated at 30° C. for 3 hours whilst stirring well and is then cooled to 0° C. and filtered.
Reaction SMILES: [C:1]1([C:7]2[N:12]3[N:13]=[N:14][N:15]=[C:11]3[N:10]3[N:16]=[CH:17][N:18]=[C:9]3[C:8]=2[CH2:19][CH2:20][OH:21])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:22]([O:25]C(=O)C)(=[O:24])[CH3:23]>N1C=CC=CC=1>[C:1]1([C:7]2[N:12]3[N:13]=[N:14][N:15]=[C:11]3[N:10]3[N:16]=[CH:17][N:18]=[C:9]3[C:8]=2[CH2:19][CH2:20][OH:21])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1.[C:22]([O-:25])(=[O:24])[CH3:23]
Reactant: CC(=O)OC(C)=O
Agent: OCCc1c(-c2ccccc2)n2nnnc2n2ncnc12
Solvent: c1ccncc1
Product: CC(=O)[O-]
Temperature: 25 °C

Procedure:
To a solution containing 2.8 g of 5-phenyltetrazolo[1,5-a][1,2,4]triazolo[1,5-c]pyrimidine-6-ethanol (0.01 mole) dissolved in 15 ml of pyridine is added 1.5 ml of acetic anhydride (0.015 mole). The reaction mixture is maintained at room temperature for 48 hours and then is evaporated to dryness yielding a crude product. The crude product is chromatographed on silica gel and recrystallized from diethyl ether to yield 5-phenyltetrazolo[1,5-a][1,2,4]triazolo[1,5-c]pyrimidine-6-ethanol, acetate (ester) having the structural formula ##STR23## and the azido tautomer thereof as a white solid having a melting point of 114° C. and the following elemental analysis: