Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][C:16]([N+:19]([O-])=O)=[CH:15][CH:14]=3)=[CH:11][CH:10]=[C:9]2[C:22]2[CH:27]=[CH:26][C:25]([N+:28]([O-])=O)=[CH:24][CH:23]=2)=[CH:4][CH:3]=1.[Cl-].[NH4+].O>C(O)C.C1COCC1.[Fe]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:9]([C:22]3[CH:27]=[CH:26][C:25]([NH2:28])=[CH:24][CH:23]=3)=[CH:10][CH:11]=[C:12]2[C:13]2[CH:18]=[CH:17][C:16]([NH2:19])=[CH:15][CH:14]=2)=[CH:4][CH:3]=1
Reactant: O=[N+]([O-])c1ccc(-c2ccc(-c3ccc([N+](=O)[O-])cc3)n2-c2ccc(F)cc2)cc1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: O
Solvent: CCO
Product: Nc1ccc(-c2ccc(-c3ccc(N)cc3)n2-c2ccc(F)cc2)cc1
Yield: 127.2 %

Procedure:
To a solution of 1-(4-fluorophenyl)-2,5-bis(4-nitrophenyl)-1H-pyrrole (1.017 g, 2.496 mmol) in ethanol (15 mL) and THF (15 mL) was added iron powder (0.836 g, 14.98 mmol) followed by ammonium chloride (0.401 g, 7.49 mmol) and water (3.75 mL). The reaction mixture was refluxed for 45 minutes. The reaction mixture was slurry filtered through diatomaceous earth and washed with ethanol. The combined filtrates were concentrated, and the residue purified by column chromatography (gradient elution from 30% to 50% EtOAc:hexanes) to provide 1.09 g (77%) of the title compound.
Reaction SMILES: [C:1]([NH:4][C:5]1[C:10]2[C:11](=[O:16])[CH2:12][CH2:13][CH2:14][CH2:15][C:9]=2[CH:8]=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[C:17]([NH:20]C1C=CC=C2C=1C(=O)CCC2)(=[O:19])[CH3:18]>>[C:1]([NH:4][C:5]1[C:10]2[C:11](=[O:16])[CH:12]([NH:20][C:17](=[O:19])[CH3:18])[CH2:13][CH2:14][CH2:15][C:9]=2[CH:8]=[CH:7][CH:6]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)Nc1cccc2c1C(=O)CCC2
Reactant: CC(=O)Nc1cccc2c1C(=O)CCCC2
Product: CC(=O)Nc1cccc2c1C(=O)C(NC(C)=O)CCC2

Procedure:
The reaction was carried out in the same manner as in Example 1-(2), except that 270 mg of the compound prepared in (2) above was used instead of 8-acetylamino-1-tetralone of Example 1-(2). The reaction mixture obtained by the post-treatment was further reacted in the same manner as in Example 1-(3) and post-treated to produce 126 mg of the title compound.
Reaction SMILES: [C:1]([NH:5][CH2:6][CH:7]([OH:26])[CH2:8][O:9][C:10]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:11]=1[C:18]1[N:23]=[N:22][C:21]([O:24]C)=[CH:20][CH:19]=1)([CH3:4])([CH3:3])[CH3:2].Cl.C(=O)([O-])[O-].[K+].[K+]>>[C:1]([NH:5][CH2:6][CH:7]([OH:26])[CH2:8][O:9][C:10]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:11]=1[C:18]1[CH:19]=[CH:20][C:21](=[O:24])[NH:22][N:23]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: COc1ccc(-c2ccc(OC)nn2)c(OCC(O)CNC(C)(C)C)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Product: COc1ccc(-c2ccc(=O)[nH]n2)c(OCC(O)CNC(C)(C)C)c1

Procedure:
6-[2-(3-t-Butylamino-2-hydroxypropoxy)-4-methoxyphenyl]-3-methoxypyridazine was hydrolysed with hydrochloric acid in a manner similar to that described in Example 3(vi). Addition of an excess of potassium carbonate to the cooled solution afforded the title compound which was recrystallised from ethanol/ether, m.p. 159°-161° C.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][O:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[C:15](=O)[CH2:14][CH2:13][CH2:12]3)[CH:5]=[CH:4][N:3]=[CH:2]1.[NH2:20][OH:21].Cl>N1C=CC=CC=1.O>[N:1]1([CH2:6][CH2:7][O:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[C:15](=[N:20][OH:21])[CH2:14][CH2:13][CH2:12]3)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: NO
Reactant: O=C1CCCc2cc(OCCn3ccnc3)ccc21
Agent: Cl
Solvent: O
Solvent: c1ccncc1
Product: ON=C1CCCc2cc(OCCn3ccnc3)ccc21
Yield: 83.2 %

Procedure:
A solution of 1.0 g (3.9 mmol) of 6-[2-(1H-1-imidazolyl)ethoxy]-1,2,3,4-tetrahydro-1-naphthalenone in 10 mL of pyridine was treated with 0.41 g (5.9 mmol) of hydroxylamine×HCl and the solution heated at reflux overnight. The solution was diluted with H2O and the product collected and dried. There was obtained 0.88 g (83% yield) of the product as a white solid, mp 177-179° C. The structure was confirmed by NMR and mass spectroscopy. MS m/z 272 (M+H+).
Reaction SMILES: C(OC(=O)[NH:7][CH2:8][C:9]1[N:10]([CH2:31][CH:32]([CH3:34])[CH3:33])[C:11](=[O:30])[C:12]2[C:17]([C:18]=1[O:19][CH2:20][CH2:21][CH2:22][CH3:23])=[CH:16][C:15]([C:24]1[S:25][CH:26]=[C:27]([CH3:29])[N:28]=1)=[CH:14][CH:13]=2)(C)(C)C.[ClH:36]>C(OCC)(=O)C>[ClH:36].[ClH:36].[NH2:7][CH2:8][C:9]1[N:10]([CH2:31][CH:32]([CH3:33])[CH3:34])[C:11](=[O:30])[C:12]2[C:17]([C:18]=1[O:19][CH2:20][CH2:21][CH2:22][CH3:23])=[CH:16][C:15]([C:24]1[S:25][CH:26]=[C:27]([CH3:29])[N:28]=1)=[CH:14][CH:13]=2
Reactant: CCCCOc1c(CNC(=O)OC(C)(C)C)n(CC(C)C)c(=O)c2ccc(-c3nc(C)cs3)cc12
Agent: Cl
Solvent: CCOC(C)=O
Product: CCCCOc1c(CN)n(CC(C)C)c(=O)c2ccc(-c3nc(C)cs3)cc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 96.4 %

Procedure:
Tert-butyl[4-butoxy-2-isobutyl-6-(4-methyl-1,3-thiazol-2-yl)-1-oxo-1,2-dihydro-3-isoquinolinyl]methylcarbamate (0.30 g, 0.6 mmol) was dissolved in a solution of 4N hydrogen chloride in ethyl acetate (5 ml) and the mixture was stirred at room temperature for 1 h. The reaction mixture was concentrated under reduced pressure, and the precipitated crystals were recrystallized from methanol-diisopropyl ether to give 3-(aminomethyl)-4-butoxy-2-isobutyl-6-(4-methyl-1,3-thiazol-2-yl)-1(2H)-isoquinolinone dihydrochloride (0.27 g, 96.4%) as crystals.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[CH:7]=[C:8]2[CH2:14][C:13](=[O:15])[NH:12][C:9]2=[N:10][CH:11]=1.[C:16]([O:19][CH:20](OCC)OCC)(=O)[CH3:17]>>[CH2:16]([O:19][CH:20]=[C:14]1[C:8]2[C:9](=[N:10][CH:11]=[C:6]([C:2]3[O:1][CH:5]=[CH:4][CH:3]=3)[CH:7]=2)[NH:12][C:13]1=[O:15])[CH3:17]
Reactant: O=C1Cc2cc(-c3ccco3)cnc2N1
Reactant: CCOC(OCC)OC(C)=O
Product: CCOC=C1C(=O)Nc2ncc(-c3ccco3)cc21

Procedure:
This compound was synthesized from 5-(2-furyl)-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one and diethoxymethyl acetate according to Procedure A. 1H NMR 400 MHz (DMSO-d6): δ10.96 (s, 1H); 8.36 (s, 1H); 7.87-7.84 (m, 2H); 7.72 (s, 1H); 6.87 (d, 1H); 6.56 (m, 1H); 4.42 (m, 2H); 1.36 (m, 3H).
Reaction SMILES: [CH2:1]([O:3][P:4]([CH2:9][C:10]([OH:12])=O)([O:6][CH2:7][CH3:8])=[O:5])[CH3:2].S(Cl)(Cl)=O.[NH2:17][C:18]1[CH:23]=[C:22]([Br:24])[CH:21]=[CH:20][C:19]=1[NH:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[CH3:40])=[O:33])=[C:28]([Cl:41])[CH:27]=1.C(N(CC)C(C)C)(C)C>C1(C)C=CC=CC=1.C(Cl)Cl>[Br:24][C:22]1[CH:21]=[CH:20][C:19]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[CH3:40])=[O:33])=[C:28]([Cl:41])[CH:27]=2)=[C:18]([NH:17][C:10](=[O:12])[CH2:9][P:4](=[O:5])([O:3][CH2:1][CH3:2])[O:6][CH2:7][CH3:8])[CH:23]=1
Reactant: CCOP(=O)(CC(=O)O)OCC
Reactant: Cc1ccccc1C(=O)c1ccc(Nc2ccc(Br)cc2N)cc1Cl
Solvent: O=S(Cl)Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCOP(=O)(CC(=O)Nc1cc(Br)ccc1Nc1ccc(C(=O)c2ccccc2C)c(Cl)c1)OCC
Temperature: 25 °C
Reaction time: 22 h

Procedure:
The reactions were conducted under an argon atmosphere using oven dried glass ware. Diethylphosphonoacetic acid (0.085 mL, 0.53 mmol) was dissolved in dry toluene (1 mL) and thionylchloride (0.044 mL, 0.61 mmol) was added. The reaction mixture was refluxed for 1 h and then concentrated in vacuo. {4-[(2-Amino-4-bromophenyl)amino]-2-chlorophenyl}(2-methylphenyl)methanone (0.28 g, 0.48 mmol)(disclosed in WO 01/05744) was dissolved in dry DCM (1 mL) and N,N-diisopropylethyl amine (0.16 mL, 0.96 mmol) was added followed by drop wise addition of the above acid chloride dissolved in dry DCM (2.5 mL). The reaction mixture was stirred at room temperature for 22 h after which it was diluted with DCM. The organic phase was washed with 10% aqueous NaHCO3, H2O and brine, dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by flash chromatography using EtOAc/petroleum ether 3:1 as the eluent to afford the title compound as an oil.
Reaction SMILES: [CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[CH2:13][O:14][C:15]1[N:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=1.[C:22](Cl)(=[O:26])[CH:23]([CH3:25])[CH3:24].C(OC(C)C)(C)C>>[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[CH2:13][O:14][C:15]1[N:20]=[CH:19][C:18]([NH:21][C:22](=[O:26])[CH:23]([CH3:25])[CH3:24])=[CH:17][CH:16]=1
Reactant: CC(C)C(=O)Cl
Reactant: Cc1onc(-c2ccccc2)c1COc1ccc(N)cn1
Solvent: CC(C)OC(C)C
Product: Cc1onc(-c2ccccc2)c1COc1ccc(NC(=O)C(C)C)cn1
Yield: 91 %

Procedure:
As described for example 179b, 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-pyridin-3-ylamine (150 mg, 0.53 mmol) was converted, using isobutyrylchloride instead of acetyl chloride, to the title compound (170 mg, 91%) which was obtained as a white solid after trituration with diisopropylether. MS: m/e=352.0 [M+H]+.
Reaction SMILES: [C:1]1([N:7]([CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])[C:8]([C:10]2[CH:11]=[C:12]3[N:18]=[C:17]([CH2:19][CH2:20][C:21]4[CH:26]=[CH:25][C:24]([C:27]#[N:28])=[CH:23][CH:22]=4)[N:16]([CH3:29])[C:13]3=[N:14][CH:15]=2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[ClH:36].C(=O)([O-])[O-].[NH4+:41].[NH4+].C(OCC)(=O)C.C(O)C.N>C(O)C>[ClH:36].[C:1]1([N:7]([CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])[C:8]([C:10]2[CH:11]=[C:12]3[N:18]=[C:17]([CH2:19][CH2:20][C:21]4[CH:22]=[CH:23][C:24]([C:27](=[NH:41])[NH2:28])=[CH:25][CH:26]=4)[N:16]([CH3:29])[C:13]3=[N:14][CH:15]=2)=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCOC(=O)CN(C(=O)c1cnc2c(c1)nc(CCc1ccc(C#N)cc1)n2C)c1ccccc1
Reactant: [NH4+]
Agent: Cl
Agent: N
Agent: O=C([O-])[O-]
Solvent: CCO
Solvent: CCOC(C)=O
Product: CCOC(=O)CN(C(=O)c1cnc2c(c1)nc(CCc1ccc(C(=N)N)cc1)n2C)c1ccccc1
Yield: 84 %

Procedure:
Prepared analogously to Example 1 from 3-methyl-2-[2-(4-cyanophenyl)ethyl]-imidazo[4,5-b]pyridin-6-yl-carboxylic acid-N-phenyl-N-ethoxycarbonylmethyl-amide, ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 84% of theory, C27H28N6O3 (484.56) Rf value: 0.44 (silica gel; ethyl acetate/ethanol/ammonia=50:45:5) EKA mass spectrum: (M+H)+ =485
Reaction SMILES: [CH3:1][O:2][P:3]([CH2:7][C:8](=[O:29])[CH:9]([N:14]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:10][CH:11]([CH3:13])[CH3:12])(=[O:6])[O:4][CH3:5].C1COCC1.[BH4-].[Na+].Cl>CO>[CH3:1][O:2][P:3]([CH2:7][CH:8]([OH:29])[CH:9]([N:14]([CH2:22][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:10][CH:11]([CH3:13])[CH3:12])(=[O:6])[O:4][CH3:5]
Reactant: COP(=O)(CC(=O)C(CC(C)C)N(Cc1ccccc1)Cc1ccccc1)OC
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: COP(=O)(CC(O)C(CC(C)C)N(Cc1ccccc1)Cc1ccccc1)OC
Temperature: -2.5 °C
Reaction time: 4 h

Procedure:
Reaction 3: A mixture of the crude oil (3-dibenzylamino-5-methyl-2-oxohexyl)-phosphonic acid dimethyl ester, i.e., compound 3, obtained in reaction 2, was dissolved in about 10% methanol and about 90% THF (v/v) and cooled at −10° C. NaBH4 (19.05 mmol) was added to the mixture in small portions with vigorous stirring. The mixture was stirred at temperature of −10 to 5° C. for 4 h and HCl 5% (v/v) was added. The reaction mixture was concentrated under reduced pressure. The residual oil was dissolved in ethyl acetate, and washed with 10 ml portions of water. The organic phase was dried over anhydrous Na2SO4 and filtered. The solvent was evaporated off to leave (3-dibenzylamino-2-hydroxy-5-methyl-hexyl)-phosphonic acid dimethyl ester, compound 4, as a crude oil. 31P NMR (at 200 MHz, CDCl3) indicated an 80:20 ratio of 2R,3S (δ 34.53) to 2S,3S (δ 35.15) isomers. (3-Dibenzylamino-2-hydroxy-5-methyl-hexyl)-phosphonic acid dimethyl ester can be isolated by chromatography or used in the next hydrogenolysis step directly without isolation.
Reaction SMILES: [Mn]([O-])(=O)(=O)=[O:2].[K+].[Br:7][CH2:8][CH2:9][CH2:10][C:11]([O:13][C:14]1[CH:19]=[C:18]([CH3:20])[CH:17]=[C:16]([CH3:21])[C:15]=1[C:22]([CH3:27])([CH3:26])[CH2:23][CH:24]=[O:25])=[O:12].Cl>O.CC(C)=O>[Br:7][CH2:8][CH2:9][CH2:10][C:11]([O:13][C:14]1[CH:19]=[C:18]([CH3:20])[CH:17]=[C:16]([CH3:21])[C:15]=1[C:22]([CH3:27])([CH3:26])[CH2:23][C:24]([OH:2])=[O:25])=[O:12]
Reactant: Cc1cc(C)c(C(C)(C)CC=O)c(OC(=O)CCCBr)c1
Reactant: O=[Mn](=O)(=O)[O-]
Agent: Cl
Agent: [K+]
Solvent: CC(C)=O
Solvent: O
Product: Cc1cc(C)c(C(C)(C)CC(=O)O)c(OC(=O)CCCBr)c1
Reaction time: 24 h
Yield: 114.9 %

Procedure:
A solution of 1 g of potassium permanganate in a mixture of 46 cm3 of distilled water and 30 cm3 of acetone is added dropwise, at 20° C., to 2.3 g of 3-[2-(4-bromobutyryloxy)4,6-dimethylphenyl]-3,3-dimethylpropanal in solution in 200 cm3 of acetone. After stirring for 24 hours, the reaction mixture is supplemented with 100 cm3 of distilled water, acidified to pH 1–2 by addition of a 1 N aqeuous hydrochloric acid solution, and then extracted with five times 100 cm3 of dichloromethane. The organic phases are combined, dried over magnesium sulfate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa). 2.7 g of 3-[2-(4-bromobutyryloxy)4,6-dimethylphenyl]-3,3-dimethylpropionic acid are obtained in the form of a colorless oil.
Reaction SMILES: Cl[C:2]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[CH2:14]([NH2:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C(O)C>[CH2:14]([NH:21][C:2]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: NCc1ccccc1
Reactant: O=C(O)c1cc([N+](=O)[O-])ccc1Cl
Solvent: CCO
Product: O=C(O)c1cc([N+](=O)[O-])ccc1NCc1ccccc1
Reaction time: 1 h
Yield: 71.1 %

Procedure:
A solution of 2-chloro-5-nitrobenzoic acid (5.0 g) and benzylamine (15.0 g) in ethanol (40 ml) is refluxed for 10 hours and then concentrated under reduced pressure. To the residue is added water (100 ml), and the resulting solution is adjusted to the pH of about 4 with acetic acid and stirred for 1 hour. The precipitate is collected and recrystallized from ethanol to give the title compound (4.8 g), mp 238°-248° C.
Reaction SMILES: C(OC1([CH2:23][C:24]2[CH:29]=[C:28]([O:30][CH3:31])[C:27]([O:32][CH3:33])=[C:26]([O:34][CH3:35])[CH:25]=2)C2C(=CC=C(C)C=2)N(CC)C1=O)(=O)C1C=CC=CC=1.[C:36]([O:44][CH:45]1[C:53]2[C:48](=[CH:49][CH:50]=[C:51]([CH3:54])[CH:52]=2)[N:47]([CH2:55][CH:56]([CH3:58])[CH3:57])[C:46]1=[O:59])(=[O:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>>[C:36]([O:44][C:45]1([CH2:23][C:24]2[CH:25]=[C:26]([O:34][CH3:35])[C:27]([O:32][CH3:33])=[C:28]([O:30][CH3:31])[CH:29]=2)[C:53]2[C:48](=[CH:49][CH:50]=[C:51]([CH3:54])[CH:52]=2)[N:47]([CH2:55][CH:56]([CH3:57])[CH3:58])[C:46]1=[O:59])(=[O:43])[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1
Reactant: CCN1C(=O)C(Cc2cc(OC)c(OC)c(OC)c2)(OC(=O)c2ccccc2)c2cc(C)ccc21
Reactant: Cc1ccc2c(c1)C(OC(=O)c1ccccc1)C(=O)N2CC(C)C
Product: COc1cc(CC2(OC(=O)c3ccccc3)C(=O)N(CC(C)C)c3ccc(C)cc32)cc(OC)c1OC

Procedure:
This compound was made in an analogous fashion to 1-ethyl-5-methyl-2-oxo-3-(3,4,5-trimethoxybenzyl)indolin-3-yl benzoate using 1-isobutyl-5-methyl-2-oxoindolin-3-yl benzoate.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:30])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][NH:15][CH2:16][CH:17]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:6]=1.[CH3:31][O:32][C:33]1[CH:34]=[C:35]([CH:38]=[C:39]([O:41][CH3:42])[CH:40]=1)[CH2:36]Br.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[CH3:1][O:2][C:3](=[O:30])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][N:15]([CH2:16][CH:17]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:36][C:35]2[CH:38]=[C:39]([O:41][CH3:42])[CH:40]=[C:33]([O:32][CH3:31])[CH:34]=2)[CH:6]=1
Reactant: COC(=O)Cc1cccc(OCCCNCC(c2ccccc2)c2ccccc2)c1
Reactant: COc1cc(CBr)cc(OC)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)Cc1cccc(OCCCN(Cc2cc(OC)cc(OC)c2)CC(c2ccccc2)c2ccccc2)c1
Temperature: 45 °C
Reaction time: 18 h
Yield: 73.2 %

Procedure:
To a solution of {3-[3-(2,2-diphenyl-ethylamino)-propoxy]-phenyl}-acetic acid methyl ester (3) (0.30 g, 0.00074 mol) in DMF (10 mL), was added 3,5-dimethoxy-benzyl bromide (0.23 g, 0.0011 mol) and powdered potassium carbonate (0.96 g, 0.007 mol), the reaction mixture was heated and stirred at 45° C. for 18 hours. After cooling, the reaction mixture was diluted with water (30 mL) and extracted with EtOAc (3×25 mL). The combined organic extracts were washed with brine (15 mL), dried over Na2SO4, concentrated to an oil, which was purified by flash chromatography (8:2 Hexanes/EtOAc) to give the desired product as oil 0.30 g in 92% yield. 1H NMR (CDCl3) δ 7.20 (m, 9H), 7.11 (t, 2H), 6.83 (d, 1H), 6.64 (s, 1H), 6.62 (d, 1H), 6.26 (s, 3H), 4.18 (t, 1H), 3.67 (s, 3H), 3.63 (s, 6H), 3.61 (s, 2H), 3.56 (s, 2H), 3.54 (t, 2H), 3.08 (d, 2H), 2.60 (t, 2H), 1.79 (t, 2H). 13C NMR (CDCl3) δ 173.3, 161.9, 160.5, 144.9, 143.8, 136.6, 130.8, 129.7, 129.6, 127.6, 122.7, 116.9, 114.5, 107.8, 100.6, 67.1, 61.2, 60.8, 56.6, 53.4, 52.0, 51.2, 42.7, 28.2.
Reaction SMILES: [Br-].[Li+].[CH2:3]([Mg]Br)[CH2:4][CH:5]=[CH2:6].[CH2:9]([C:13]1[CH2:17][CH2:16][C:15](=[O:18])[CH:14]=1)[CH2:10][CH:11]=[CH2:12]>O1CCCC1.[Cu]I>[CH2:3]([C:13]1([CH2:9][CH2:10][CH:11]=[CH2:12])[CH2:17][CH2:16][C:15](=[O:18])[CH2:14]1)[CH2:4][CH:5]=[CH2:6]
Reactant: C=CCC[Mg]Br
Reactant: C=CCCC1=CC(=O)CC1
Agent: [Cu]I
Agent: [Br-]
Agent: [Li+]
Solvent: C1CCOC1
Product: C=CCCC1(CCC=C)CCC(=O)C1
Temperature: -78 °C
Reaction time: 0.67 h

Procedure:
To a suspension of copper(I) iodide (2.6 g) and lithium bromide (1.2 g) in tetrahydrofuran (25 mL) was added dropwise a 0.5M tetrahydrofuran solution of 3-butenylmagnesium bromide (26.5 mL) under nitrogen atmosphere at −78° C. over 6 minutes, followed by stirring the reaction mixture at −78° C. for 40 minutes. Then, 5 minutes after addition of boron trifluoride diethyl ether complex (0.554 mL), to the reaction mixture was added 3-(3-butenyl)cyclopent-2-enone (0.6 g) obtained in Step 1. Half an hour later, after addition of boron trifluoride diethyl ether complex (0.250 mL), the reaction mixture was stirred at −78° C. for 2 hours, and further stirred at room temperature overnight after removing a dry-ice/ethanol bath. Then, after addition of saturated aqueous ammonium chloride solution and 28% aqueous ammonia solution, the reaction mixture was extracted with ethyl acetate. The organic layer was washed successively with aqueous ammonia solution and saturated brine, dried and concentrated. The residue was purified by column chromatography on silica gel to give 3,3-dibut-3-enylcyclopentanone (380 mg).
Reaction SMILES: [CH3:1][N:2]1[CH:6]2[CH2:7][C:8]([CH2:10][CH:3]1[CH2:4][CH2:5]2)=[O:9].[Li+].[BH4-].[OH-].[Na+]>C1COCC1>[CH3:1][N:2]1[C@@H:6]2[CH2:7][C@H:8]([OH:9])[CH2:10][C@H:3]1[CH2:4][CH2:5]2
Reactant: CN1C2CCC1CC(=O)C2
Agent: [BH4-]
Agent: [Li+]
Agent: [Na+]
Solvent: C1CCOC1
Product: CN1[C@@H]2CC[C@H]1C[C@H](O)C2
Temperature: -78 °C
Reaction time: 6 h
Yield: 84.6 %

Procedure:
Tropinone (3.0 g, 21.6 mmole) was placed in a dry 250 mL round bottom flask, purged with argon. Anhydrous THF (75 mL, w/o stabilizer) was added and the solution was cooled in a dry ice/acetone bath to -78° C. In another dry, argon purged flask LiBH4 (1.41 g, 64.6 mmole) was dissolved in anhydrous THF (50 mL) and cooled to -78° C. The contents of this flask was transferred to the first flask via cannula, under argon. This flask was rinsed once with additional THF (25 mL). The reaction was allowed to proceed for 6 hours at -78° C. and then warmed gradually to room temperature overnight. The reaction mixture was cooled in an ice water bath and carefully quenched with H2O (10 mL) followed by neutralization with 2.8N HCl. The volatiles were removed in vacuo and the residue was taken up in 1N HCl (100 mL) and heated to reflux for 60 min to dissociate the pseudotropine-boron complex formed. The acidic solution was adjusted to pH=10-11 with 15% NaOH and extracted with CHCl3 /2-propanol (3:1, 10×50 mL). The organic fractions were combined, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo resulting in 2.58 g (85% yield) of a white solid product. Recrystallization from toluene/pet ether gave small white needles, mp 106°-109° C. (mp 109° C., The Merck Index, 11th Edition, 1989, #7937, p. 1259).
Reaction SMILES: [CH2:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:7]([Br:11])([CH3:10])([CH3:9])[CH3:8].[Br-].[Al+3].[Br-].[Br-]>O>[Br:11][C:7]12[CH2:10][CH:3]3[CH2:4][CH:5]([CH2:6][C:1]([CH2:6][CH2:1][CH2:2][CH3:3])([CH2:2]3)[CH2:8]1)[CH2:9]2
Reactant: CC(C)(C)Br
Reactant: C1CCCCC1
Agent: [Al+3]
Agent: [Br-]
Solvent: O
Product: CCCCC12CC3CC(CC(Br)(C3)C1)C2
Reaction time: 2 h

Procedure:
Into a 200 ml egg plant-shaped flask, 8.8 g (0.046 moles) of 1-(n-butyl)adamantane obtained above was weighed and placed. Under the stream of nitrogen gas, 100 ml of cyclohexane was added, and a solution was prepared. While the solution was kept at 0° C. in an ice bath, 8.8 g (0.063 moles) of t-butyl bromide and 0.4 g (0.0014 moles) of aluminum bromide were added, and the reaction was allowed to proceed for 2 hours. To the reaction fluid, 100 ml of ion-exchanged water was added, and the extraction with cyclohexane was conducted using a separation funnel. The solvent was removed using an evaporator, and 10.4 g of 1-bromo-3-(n-butyl)adamantane of the object compound was obtained as a colorless transparent liquid substance (the yield: 84%).
Reaction SMILES: [C:1]([OH:5])([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.[C:12]([C:14]1[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=1)[C:17](Cl)=[O:18])#[N:13]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:1]([O:5][C:17](=[O:18])[C:16]1[CH:20]=[CH:21][CH:22]=[C:14]([C:12]#[N:13])[CH:15]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)O
Reactant: N#Cc1cccc(C(=O)Cl)c1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(C)(C)OC(=O)c1cccc(C#N)c1
Temperature: 25 °C
Reaction time: 20 h
Yield: 81.9 %

Procedure:
Part B. To a mixture of tert-butanol (3.50 g, 47.22 mmol), pyridine (3.72 g, 46.78 mmol) and cat. DMAP in methylene chloride (15 mL) is added dropwise 3-cyanobenzoyl chloride (6.81 g, 41.07 mmol) and pyridine (3 mL) in methylene chloride (10 mL) at 0° C. The resulting mixture is stirred at room temperature for 20 h. The solvent is evaporated, and the residue is purified by flash chromatography (1:1 methylene chloride/hexanes) to afford 3-cyano-benzoic acid tert-butyl ester (6.84 g, 82.1% yield) as white solid. 1H NMR (300 MHz, CDCl3): δ 8.24 (1H, s), 8.20 (1H, dd, J=7.9, 1.2 Hz), 7.78 (1H, dd, J=6.7, 1.1 Hz), 7.52 (1H, m), 1.58 (9H, s).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16](I)[S:17][C:13]=2[N:12]2[C:19]([CH3:22])=[N:20][N:21]=[C:11]2[CH2:10][N:9]=1.[CH2:23]([N:26]1[C:34]2[C:29]3[C:30](=[CH:35][CH:36]=[CH:37][C:28]=3[C:27]1=[O:38])[CH:31]=[CH:32][CH:33]=2)[C:24]#[CH:25].O.Cl>C(OCC)(=O)C>[ClH:1].[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([C:25]#[C:24][CH2:23][N:26]3[C:34]4[C:29]5[C:30](=[CH:35][CH:36]=[CH:37][C:28]=5[C:27]3=[O:38])[CH:31]=[CH:32][CH:33]=4)[S:17][C:13]=2[N:12]2[C:19]([CH3:22])=[N:20][N:21]=[C:11]2[CH2:10][N:9]=1
Reactant: C#CCN1C(=O)c2cccc3cccc1c23
Reactant: Cc1nnc2n1-c1sc(I)cc1C(c1ccccc1Cl)=NC2
Agent: Cl
Solvent: CCOC(C)=O
Solvent: O
Product: Cc1nnc2n1-c1sc(C#CCN3C(=O)c4cccc5cccc3c45)cc1C(c1ccccc1Cl)=NC2

Procedure:
Reaction of 4-(2-chlorophenyl)-2-iodo-9-methyl-6H-thieno[3,2-f][1,2,4] triazolo[4,3-a][1,4]diazepine with 1-(2-propynyl)-benz[cd]indol-2(1H)-one as described in Example 37 yielded after chromatographic purification and slow crystallization from ethyl acetate yellow crystals with m.p. 202°-205° C. These crystals contained according to analytical data 0.75 mol of water. Treatment of this product with ethanolic hydrogen chloride and addition of ethyl acetate gave a crystalline hydrochloride of the title compound with m.p. 219°-222° C.