Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6](=[O:26])[NH:7][C:8]1[CH:13]=[C:12]([O:14][C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-])=O)=[CH:17][N:16]=2)[C:11]([F:24])=[CH:10][C:9]=1[F:25])([CH3:4])([CH3:3])[CH3:2].O1CCCC1>CO.[C].[Pd]>[C:1]([O:5][C:6](=[O:26])[NH:7][C:8]1[CH:13]=[C:12]([O:14][C:15]2[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][N:16]=2)[C:11]([F:24])=[CH:10][C:9]=1[F:25])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)Nc1cc(Oc2ccc([N+](=O)[O-])cn2)c(F)cc1F
Agent: [Pd]
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)Nc1cc(Oc2ccc(N)cn2)c(F)cc1F
Temperature: 25 °C
Reaction time: 8 h
Yield: 93.8 %

Procedure:
A suspension of tert-butyl{2,4-difluoro-5-[(5-nitropyridin-2-yl)oxy]phenyl}carbamate (10.10 g, 27.5 mmol) and 10% palladium-carbon (5.0 g) in methanol (50 mL)-tetrahydrofuran (50 mL) was vigorously stirred at room temperature under a hydrogen atmosphere overnight. The insoluble material was filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was poured into water (200 mL), and the mixture was extracted with ethyl acetate (100 mL×2). The ethyl acetate layers were combined dried over anhydrous sodium sulfate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the residue was crystallized from acetonitrile to give the title compound (8.70 g, 94%) as a white powder.
Reaction SMILES: Cl[C:2]1[N:7]2[N:8]=[C:9]([NH:11][C:12](=[O:19])[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1.[CH3:20][O:21][CH2:22][CH2:23][CH2:24][NH2:25]>C1COCC1>[CH3:20][O:21][CH2:22][CH2:23][CH2:24][NH:25][C:2]1[N:7]2[N:8]=[C:9]([NH:11][C:12](=[O:19])[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1
Reactant: COCCCN
Reactant: O=C(Nc1nc2cccc(Cl)n2n1)c1ccccc1
Solvent: C1CCOC1
Product: COCCCNc1cccc2nc(NC(=O)c3ccccc3)nn12

Procedure:
The title compound was prepared following procedure described for example 30 but starting from N-(5-chloro[1,2,4]triazolo[1,5-a]pyridin-2-yl)benzamide ((B3), 50 mg; 0.18 mmol; 1.0 eq.) and 3-methoxypropylamine (195 μl; 1.91 mmol; 10.0 eq.) in THF (3.0 mL), 90° C., 12 h, as white needles (35 mg; 56%). HPLC, Rt: 1.95 min. (purity 99.3%). LC/MS, M+(ESI): 326.2.
Reaction SMILES: [Cl:1][SiH2:2][Cl:3].[CH2:4]=[CH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>[H+].[H+].Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl.C(O)(C)C>[CH2:4]([Si:2]([CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)([Cl:3])[Cl:1])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: C=Cc1ccccc1
Reactant: Cl[SiH2]Cl
Agent: Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl
Agent: [H+]
Solvent: CC(C)O
Product: Cl[Si](Cl)(CCc1ccccc1)CCc1ccccc1
Temperature: 50 °C

Procedure:
30.0 g (300 millimol) of dichlorosilane, 56.5 g (543 millimol) of styrene and 50 ml of an isopropanol solution of chloroplatinic acid [H2PtCl6.6H2O (4.83×10-6 mol)] were charged in a 200 ml pressure-proof stainless steel reaction tube and reaction was carried out as in example 3 by heating in an oil bath at 50° C. for 15 hours with stirring. After reaction, the reacted liquid resinified and no diphenethyldichlorosilane was obtained.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C@H:9]([NH:11][CH:12]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([N+:19]([O-])=O)[CH:14]=2)[CH3:10])[CH:5]=[CH:6][C:7]=1[F:8].[BH4-].[Na+]>O.O.O.O.O.O.[Ni](Cl)Cl.CO>[F:1][C:2]1[CH:3]=[C:4]([C@H:9]([NH:11][CH:12]([C:22]2[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=2)[C:13]2[CH:14]=[C:15]([NH2:19])[CH:16]=[CH:17][CH:18]=2)[CH3:10])[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: C[C@@H](NC(c1ccc(F)cc1)c1cccc([N+](=O)[O-])c1)c1ccc(F)c(F)c1
Agent: Cl[Ni]Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: C[C@@H](NC(c1ccc(F)cc1)c1cccc(N)c1)c1ccc(F)c(F)c1

Procedure:
Following a similar reaction, separation and purification procedure to that described in Example (59b), 18.44 g of N-[(R)-1-(3,4-difluorophenyl)ethyl]-N-[(4-fluorophenyl)-(3-nitrophenyl)methyl]amine, 22.69 g of nickel chloride hexahydrate, 7.22 g of sodium borohydride and 150 ml of methanol were reacted, to obtain 1.27 g of isomer A and 2.79 g of isomer B of the title compound, respectively, each as a pale yellow oil.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([S:9][C:10]2[N:14]([CH2:15][O:16][CH2:17][CH2:18][OH:19])[C:13]([CH3:20])=[N:12][C:11]=2[CH:21]([CH3:23])[CH3:22])[CH:5]=[C:6]([CH3:8])[CH:7]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1.[CH3:43][O:44][C:45]1[CH2:49][CH2:48][CH2:47][CH:46]=1>C(Cl)Cl.C(N(CC)CC)C>[CH3:8][C:6]1[CH:5]=[C:4]([S:9][C:10]2[N:14]([CH2:15][O:16][CH2:17][CH2:18][O:19][C:45]3([O:44][CH3:43])[CH2:49][CH2:48][CH2:47][CH2:46]3)[C:13]([CH3:20])=[N:12][C:11]=2[CH:21]([CH3:23])[CH3:22])[CH:3]=[C:2]([CH3:1])[CH:7]=1
Reactant: Cc1cc(C)cc(Sc2c(C(C)C)nc(C)n2COCCO)c1
Reactant: COC1=CCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Solvent: O
Product: COC1(OCCOCn2c(C)nc(C(C)C)c2Sc2cc(C)cc(C)c2)CCCC1
Reaction time: 2 h
Yield: 80.9 %

Procedure:
A solution of the compound 1 (33.4 mg, 0.1 mmol) and p-toluenesulfonic acid hydrate (20.4 mg, 0.108 mmol) in a mixture of methylene chloride (1 mL) -toluene (0.1 mL) was concentrated under reduced pressure. Trhe obtained residue was dissolved in methylene chloride (1 mL), to which was added 1-methoxycyclopentene (98.5 mg, 1 mmol), and the mixture was stirred for 2 hours. Triethylamine was added to the reaction mixture, and the mixture was concentrated under reduced pressure. The residue was purified by chromatography on an alumina column (eluate: hexane - ethyl acetate (2:1)) to give the same compound 2 (35 mg, 81 %) as the Example 1.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][CH:13]2[CH2:17][C:16]3[CH:18]=[CH:19][CH:20]=[C:21](Br)[C:15]=3[O:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[Cl:23][C:24]1[CH:25]=[CH:26][C:27]([CH3:33])=[C:28](B(O)O)[CH:29]=1>>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][CH:13]2[CH2:17][C:16]3[CH:18]=[CH:19][CH:20]=[C:21]([C:26]4[CH:25]=[C:24]([Cl:23])[CH:29]=[CH:28][C:27]=4[CH3:33])[C:15]=3[O:14]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: Cc1ccc(Cl)cc1B(O)O
Reactant: Cc1ccc(S(=O)(=O)OCC2Cc3cccc(Br)c3O2)cc1
Product: Cc1ccc(S(=O)(=O)OCC2Cc3cccc(-c4cc(Cl)ccc4C)c3O2)cc1
Yield: 80.6 %

Procedure:
Treatment of (±)-(7-bromo-2,3-dihydro-1-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.305 mmol) with (5-chloro-2-methylphenyl)boronic acid (0.334 g, 1.96 mmol) generally according to the procedure described for Intermediate 184 provided 0.451 g (81%) of (±)-[7-(5-chloro-2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a white solid. Rf=0.43 (silica, ethyl acetate:hexanes 1:4).
Reaction SMILES: C[O:2][C:3](=O)[C@:4]1([OH:19])[CH2:8][CH2:7][CH2:6][N:5]1[S:9]([C:12]1[CH:18]=[CH:17][C:15]([CH3:16])=[CH:14][CH:13]=1)(=[O:11])=[O:10].Cl>C1COCC1>[S:9]([N:5]1[CH2:6][CH2:7][CH2:8][C@@:4]1([OH:19])[CH2:3][OH:2])([C:12]1[CH:13]=[CH:14][C:15]([CH3:16])=[CH:17][CH:18]=1)(=[O:10])=[O:11]
Reactant: COC(=O)[C@]1(O)CCCN1S(=O)(=O)c1ccc(C)cc1
Agent: Cl
Solvent: C1CCOC1
Product: Cc1ccc(S(=O)(=O)N2CCC[C@@]2(O)CO)cc1
Temperature: -20 °C
Reaction time: 18 h
Yield: 89.7 %

Procedure:
To a solution of N-tosylhydroxy-L-proline methyl ester (62.20 g) in THF (600 mL) at 0° C. for 1 h and allowed to stand at 23° C. for 18 h. The reaction mixture was cooled to -20° C., made neutral with 6N HCl, and concentrated under reduced pressure. The residue was treated with water (550 mL) and extracted with EtOAc (4×300 mL). The combined organic extracts were washed with H2O, dried over MgSO4, filtered, and concentrated under reduced pressure to give N-tosylhydroxy-L-prolinol as a white solid (50.56 g, 88.8%) which was used in the next step without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[O:9][N:10]=[C:11]3[CH:16]=[CH:15][C:14]([C:17]([C:19]4[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=4)=[O:18])=[CH:13][C:12]=23)[CH:5]=[CH:6][CH:7]=1>C1COCC1.O>[NH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17](=[O:18])[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)=[CH:13][C:12]=1[C:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=1)=[O:9]
Reactant: O=C(c1ccc(F)cc1)c1ccc2noc(-c3cccc(Cl)c3)c2c1
Solvent: O
Solvent: C1CCOC1
Product: Nc1ccc(C(=O)c2ccc(F)cc2)cc1C(=O)c1cccc(Cl)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 100.1 %

Procedure:
A mixture of intermediate 2 (0.0514 mol) in THF (180 ml) was cooled on an ice bath. TiCl3 15% in water (180 ml) was added dropwise slowly. The mixture was stirred at room temperature overnight, then poured out into ice water and extracted with DCM. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated till dryness, yielding 18.2 g (100%) of [2-amino-5-(4-fluorobenzoyl)phenyl](3-chlorophenyl)-methanone (intermediate 3).
Reaction SMILES: [CH3:1][C:2]1[C:14]([CH3:15])=[CH:13][C:5]2[NH:6][C:7]([C:9]([F:12])([F:11])[F:10])=[N:8][C:4]=2[CH:3]=1.[H-].[Na+].[CH3:18][O:19][C:20](=[O:29])[C:21]1[CH:26]=[CH:25][C:24]([CH2:27]Br)=[CH:23][CH:22]=1>CN(C=O)C>[CH3:18][O:19][C:20](=[O:29])[C:21]1[CH:26]=[CH:25][C:24]([CH2:27][N:8]2[C:4]3[CH:3]=[C:2]([CH3:1])[C:14]([CH3:15])=[CH:13][C:5]=3[N:6]=[C:7]2[C:9]([F:12])([F:10])[F:11])=[CH:23][CH:22]=1
Reactant: Cc1cc2nc(C(F)(F)F)[nH]c2cc1C
Reactant: COC(=O)c1ccc(CBr)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(Cn2c(C(F)(F)F)nc3cc(C)c(C)cc32)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 23.5 %

Procedure:
5,6-Dimethyl-2-trifluoromethyl-1H-benzoimidazole (2.14 g, 0.01 mol) was dissolved in DMF (50 mL). Sodium hydride (60% dispersion in oil, 0.48 g, 0.012 mol) was added and the reaction mixture was stirred at ambient temperature for 0.5 hour under an atmosphere of nitrogen. 4-Bromomethyl benzoic acid methyl ester (2.29 g, 0.01 mol) was then added. The mixture was stirred at 80° C. for 18 hours. Most of the solvent was evaporated. The residue was diluted with water and extracted with ethyl acetate. The organic phase was washed with water, dried over anhydrous sodium sulfate then evaporated. The residue was crystallized from ethyl acetate/hexane twice to afford pure title compound (0.85 g, 23.5% yield) as a white solid, m.p. 150°-152° C. Anal. Calcd. for C19H17F3N2O2 : C, 62.98; H, 4.73; N, 7.73. Found: C, 62.96; H, 4.73; N, 7.56. Mass spectrum (+FAB; [M+H]+) 363. 1H-NMR (DMSO-d6; 400 MHz) δ 7.90 (d, 1H), 7.63 (s, 1H), 7.45 (s, 1H), 7.15 (d, 2H), 5.74 (2H), 3.81 (s, 3H), 2.33 (s, 3H), and 2.30 ppm (s, 3H).
Reaction SMILES: Br[CH2:2][CH:3]=[C:4]1[CH2:7][CH2:6][CH2:5]1.[C:8]1([S:14]([O-:16])=[O:15])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[Na+]>>[C:4]1(=[CH:3][CH2:2][S:14]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)(=[O:16])=[O:15])[CH2:7][CH2:6][CH2:5]1
Reactant: O=S([O-])c1ccccc1
Reactant: BrCC=C1CCC1
Agent: [Na+]
Product: O=S(=O)(CC=C1CCC1)c1ccccc1

Procedure:
Using the procedure of Example I, 1-bromo-2-cyclobutylidene-ethane was reacted with sodium phenyl sulfinate to form (2-cyclobutylidene-ethyl)-phenyl sulfone having a melting point of 76° to 78° C which was then reacted with ethyl β,β-dimethylacrylate to form ethyl dl-trans 3,3-dimethyl-2-cyclobutylidenemethyl-cyclopropanecarboxylate. The said ethyl ester was hydrolyzed under alkaline conditions to form dl-trans 3,3-dimethyl-2-cyclobutylidenemethyl-cyclopropanecarboxylic acid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([CH:12]=[CH:13][CH:14]=[CH:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:6]2.[H-].[Na+].[Cl:23][C:24]1[CH:32]=[CH:31][C:27]([C:28](Cl)=[O:29])=[CH:26][CH:25]=1>O1CCCC1>[Cl:23][C:24]1[CH:32]=[CH:31][C:27]([C:28]([N:8]2[C:9]3[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:11][CH:10]=3)[CH:6]=[C:7]2[CH:12]=[CH:13][CH:14]=[CH:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[O:29])=[CH:26][CH:25]=1
Reactant: O=C(Cl)c1ccc(Cl)cc1
Reactant: CCOC(=O)C=CC=Cc1cc2cc(OC)ccc2[nH]1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)C=CC=Cc1cc2cc(OC)ccc2n1C(=O)c1ccc(Cl)cc1
Temperature: 0 °C
Yield: 63.1 %

Procedure:
A solution of ethyl 5-(5-methoxyindol-2-yl)-2,4-pentadienoate (0.8 g, 2.9 mmol) in 20 ml of tetrahydrofuran (THF) was added dropwise to a suspension of sodium hydride (0.024 g of a 60% reagent) at 0° C. (ice bath). After addition, the mixture was stirred in the ice bath for 1 hour and a solution of p-chlorobenzoyl chloride (0.54 g) in 10 ml of THF was added; the resulting mixture was filtered to remove the precipitate and the filtrate was washed with brine, dried (magnesium sulfate) and concentrated on rotary evaporator to give a yellow oil. Crystallization of this oily substance from acetone-ether afforded 0.75 g of ethyl 5-(1-p-chlorobenzoyl-5-methoxyindol-2-yl)-2,4-pentadienoate as yellow powders, m.p., 121°-125° C. MS(EI): 40 g(M+), 336 (M+ --CO2Et).
Reaction SMILES: C([O:8][C:9]1[N:10]([C:19]2[N:20]=[C:21]([NH2:27])[NH:22][C:23](=[O:26])[C:24]=2[N:25]=1)[C@@H:11]1[O:18][C@H:15]([CH2:16][OH:17])[C@@H:13]([OH:14])[CH2:12]1)C1C=CC=CC=1>CO.O.[Pd]>[OH:8][C:9]1[N:10]([C:19]2[N:20]=[C:21]([NH2:27])[NH:22][C:23](=[O:26])[C:24]=2[N:25]=1)[C@@H:11]1[O:18][C@H:15]([CH2:16][OH:17])[C@@H:13]([OH:14])[CH2:12]1
Reactant: Nc1nc2c(nc(OCc3ccccc3)n2[C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]1
Agent: [Pd]
Solvent: CO
Solvent: O
Product: Nc1nc2c(nc(O)n2[C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]1

Procedure:
The final stage of the synthesis is accomplished according to the published procedure of Lin et al. (J. Med. Chem. 28:1194-1198, 1985). A solution of 8-(benzyloxy)-2'-deoxyguanosine (0.20 g, 0.54 mmol) in a mixture of methanol (8 mL) and water (8 mL) is hydrogenated over 10% palladium on carbon (0.3 g) at 50 psi and room temperature for 18 hours. The catalyst is removed by filtration and the solvent evaporated to dryness to yield 8-hydroxydeoxyguanosine.
Reaction SMILES: [CH3:1][CH:2]([C:6](=[O:8])[CH3:7])[C:3](=[O:5])[CH3:4].[C:9]([O:13][CH2:14][CH3:15])(=[O:12])[CH:10]=[CH2:11]>N12CCCN=C1CCCCC2.C(OCC)C>[CH2:14]([O:13][C:9](=[O:12])[CH2:10][CH2:11][C:2]([C:6](=[O:8])[CH3:7])([CH3:1])[C:3](=[O:5])[CH3:4])[CH3:15]
Reactant: CC(=O)C(C)C(C)=O
Reactant: C=CC(=O)OCC
Solvent: C1CCC2=NCCCN2CC1
Solvent: CCOCC
Product: CCOC(=O)CCC(C)(C(C)=O)C(C)=O
Reaction time: 16 h
Yield: 59.3 %

Procedure:
30 g of 3-methyl-2,4-pentandione and 0.4 g of 1,8-diazabicyclo-[5.4.0]-undec-7-ene were mixed and 39.3 g of ethyl acrylate was added dropwise with the temperature being controlled by cooling with ice. Stirring was continued for 16 hours, the base was neutralized, 50 ml of diethyl ether was added, and the mixture was extracted with an aqueous sodium carbonate solution and water. Fractional distillation of the organic layer yielded 33.4 g of 4-acetyl-4-methyl-5-oxo-hexanoic acid ethyl ester (boiling point: 95° C./0.02 mbar; purity: 98%; colorless).
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:17]=[C:18]5[C:22](=[CH:23][CH:24]=4)[N:21]([CH2:25][CH2:26][CH2:27][C:28]([OH:30])=[O:29])[CH:20]([C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:19]5)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1>C(#N)C.O.FC(C(O)=O)(F)F>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:17]=[C:18]5[C:22](=[CH:23][CH:24]=4)[N:21]([CH2:25][CH2:26][CH2:27][C:28]([OH:30])=[O:29])[C:20]([C:31]([CH3:34])([CH3:33])[CH3:32])=[CH:19]5)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1
Reactant: CC(C)(C)C1Cc2cc(NC(=O)C3(c4ccc5c(c4)OCO5)CC3)ccc2N1CCCC(=O)O
Solvent: CC#N
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: CC(C)(C)c1cc2cc(NC(=O)C3(c4ccc5c(c4)OCO5)CC3)ccc2n1CCCC(=O)O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
4-(5-(1-(Benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2-tert-butyl indolin-1-yl)butanoic acid (130 mg, 0.28 mmol) was taken up in a mixture of acetonitrile-H2O-TFA. The solvent was removed under reduced pressure and the residue obtained was dissolved in CDCl3. After a brief exposition to daylight (5-10 min), the solution turned purple. The mixture was stirred open to the atmosphere at room temperature until complete disappearance of the starting material (8 h). Solvent was removed under reduced pressure and the residue was purified by reverse phrase HPLC to give 4-(5-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2-tert-butyl-1H-indol-1-yl)butanoic acid. 1H NMR (400 MHz, CDCl3) δ 7.52 (d, J=1.9 Hz, 1H), 7.18 (d, J=2.1 Hz, 1H), 7.16 (s, 1H), 7.03 (dd, J=9.4, 1.9 Hz, 1H), 7.00-6.98 (m, 2H), 6.85 (d, J=7.9 Hz, 1H), 6.16 (s, 1H), 6.02 (s, 2H), 4.29-4.24 (m, 2H), 2.48 (dd, J=6.9, 6.9 Hz, 2H), 2.12-2.04 (m, 2H), 1.69 (dd, J=6.8, 3.7 Hz, 2H), 1.43 (s, 9H), 1.09 (dd, J=6.8, 3.7 Hz, 2H). MS (ESI) m/e (M+H+) 463.0.
Reaction SMILES: [O:1]=[C:2]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])/[CH:3]=[CH:4]/[C@H:5]1[C@H:12]([O:13][C:14](=[O:27])[C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:17][CH:16]=2)[CH2:11][C@H:10]2[C@@H:6]1[CH2:7][C:8](=[O:28])[O:9]2.CO.[Cl-].[Ce+3].[Cl-].[Cl-].[BH4-].[Na+]>C1COCC1>[OH:1][C@@H:2]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])/[CH:3]=[CH:4]/[C@H:5]1[C@H:12]([O:13][C:14](=[O:27])[C:15]2[CH:16]=[CH:17][C:18]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)=[CH:19][CH:20]=2)[CH2:11][C@H:10]2[C@@H:6]1[CH2:7][C:8](=[O:28])[O:9]2
Reactant: CCCCCCCC(=O)/C=C/[C@@H]1[C@H]2CC(=O)O[C@H]2C[C@H]1OC(=O)c1ccc(-c2ccccc2)cc1
Agent: [BH4-]
Agent: [Ce+3]
Agent: [Cl-]
Solvent: CO
Solvent: C1CCOC1
Product: CCCCCCC[C@H](O)/C=C/[C@@H]1[C@H]2CC(=O)O[C@H]2C[C@H]1OC(=O)c1ccc(-c2ccccc2)cc1
Reaction time: 0.08 h

Procedure:
The unsaturated ketone (3) (3.03 g) was dissolved into a mixed solvent of methanol (60 ml) and THF (7 ml). Into the obtained solution cerium (III) chloride.7H2O (2.38 g) was added at −20° C., and stirred at the same temperature for 10 minutes, into which sodium borohydride (0.25 g) was added and stirred for 5 minutes. A crude compound obtained by a usual work-up was purified using a column chromatography to give the title compound (4a) as a compound having a lower polarity and the 3R-hydroxy compound (4b) of the title compound (4a) as a compound having a higher polarity. Yield: 4.58 9 (4a:3S-hydroxy compound)
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=2[N:16]([CH3:21])[CH2:17][CH2:18][C:19]#[N:20])[C:5]([Cl:22])=[CH:4][N:3]=1.[NH2:23][C:24]1[CH:25]=[CH:26][C:27]2[C:33]([CH3:35])([CH3:34])[CH2:32][CH2:31][C:30](=[O:36])[N:29]([CH2:37][CH3:38])[C:28]=2[CH:39]=1>>[Cl:22][C:5]1[C:6]([NH:8][C:9]2[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=2[N:16]([CH3:21])[CH2:17][CH2:18][C:19]#[N:20])=[N:7][C:2]([NH:23][C:24]2[CH:25]=[CH:26][C:27]3[C:33]([CH3:34])([CH3:35])[CH2:32][CH2:31][C:30](=[O:36])[N:29]([CH2:37][CH3:38])[C:28]=3[CH:39]=2)=[N:3][CH:4]=1
Reactant: CN(CCC#N)c1cccc(F)c1Nc1nc(Cl)ncc1Cl
Reactant: CCN1C(=O)CCC(C)(C)c2ccc(N)cc21
Product: CCN1C(=O)CCC(C)(C)c2ccc(Nc3ncc(Cl)c(Nc4c(F)cccc4N(C)CCC#N)n3)cc21

Procedure:
Title compound was prepared from 3-{[2-(2,5-Dichloro-pyrimidin-4-ylamino)-3-fluoro-phenyl]-methyl-amino}-propionitrile and 8-Amino-1-ethyl-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one in an analogous manner to Example 1221d. Title compound isolated as a white lyophilate (82 mg, 61%). HPLC 99% purity, LCMS 538.20 (M+H), 1H-NMR (CDCl3, 400 MHz) δ 12.10 (s, 1H), 7.93 (s, 1H), 7.76 (s, 1H), 7.44 (s, 1H), 7.38-7.32 (m, 1H), 7.21 (m, 2H), 6.99-6.92 (m, 2H), 3.70-3.60 (m, 2H), 3.26 (t, J=6.5 Hz, 2H), 2.69 (s, 3H), 2.52 (t, J=6.4 Hz, 2H), 2.24-2.20 (m, 2H), 2.10-1.98 (m, 2H), 1.32 (s, 6H), 1.09 (t, J=7.4 Hz, 3H).
Reaction SMILES: [C:1]([CH2:3][CH2:4][OH:5])#[N:2].[CH3:6][O:7][P:8](O)[OH:9].[Cl-].[CH:12]([N-:15][CH:16]([CH3:18])[CH3:17])([CH3:14])[CH3:13].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[CH:12]([N-:15][CH:16]([CH3:18])[CH3:17])([CH3:14])[CH3:13].[C:1]([CH2:3][CH2:4][O:5][P:8]([OH:9])[O:7][CH3:6])#[N:2]
Reactant: COP(O)O
Reactant: N#CCCO
Agent: CC(C)[N-]C(C)C
Agent: [Cl-]
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COP(O)OCCC#N

Procedure:
0.68 ml (10 mmol) of 2-cyanoethanol are reacted analogously to Example 2 with 2 ml (11 mmol) of phosphorous acid methyl ester-diisopropylamide-chloride in the presence of 8 ml of diisopropylethylamine in 20 ml of freshly distilled methylene chloride. Drying at 30° C. in a high vacuum gives 2.5 g of an oil which, according to 31P-NMR, contains 94% of the compound VIII. ##STR15##
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH2:13][CH:12]([OH:14])[CH2:11]2)=[N:8][CH:9]=1)([O-:3])=[O:2].[H-].[Na+].[CH3:17]I>>[CH3:17][O:14][CH:12]1[CH2:11][N:10]([C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][N:8]=2)[CH2:13]1
Reactant: O=[N+]([O-])c1ccc(N2CC(O)C2)nc1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Product: COC1CN(c2ccc([N+](=O)[O-])cn2)C1
Yield: 119.5 %

Procedure:
1-(5-Nitro-pyridin-2-yl)-azetidin-3-ol (97.5 mg, 0.5 mmol) was treated with 60% NaH in oil (40 mg, 1 mmol) and methyl iodide (125 uL, 2 mmol) as above to yield 125 mg of crude product that was used without further purification. ES-MS calcd for C9H11N3O3 (m/e) 209.21, obsd 210 (M+H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([NH2:11])[C:5]2[CH:6]=[N:7][NH:8][C:9]=2[CH:10]=1.[H-].[Na+].I[CH2:15][CH3:16]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH2:11])[C:5]2[CH:6]=[N:7][N:8]([CH2:15][CH3:16])[C:9]=2[CH:10]=1
Reactant: CCI
Reactant: Nc1cc(Br)cc2[nH]ncc12
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCn1ncc2c(N)cc(Br)cc21
Reaction time: 0.25 h
Yield: 32.5 %

Procedure:
To a solution of 6-bromo-1H-indazol-4-amine (available from Sinova, 300 mg, 1.41 mmol) in THF (7 ml), cooled to 0° C. was added 60% sodium hydride in mineral oil (62 mg, 1.55 mmol) and the reaction was stirred for 15 mins. Iodoethane (0.124 ml, 1.55 mmol) was added and the reaction was stirred overnight. The reaction was quenched with MeOH (1 ml), diluted with water (10 ml), then extracted into ethyl acetate, which was separated and evaporated to dryness. The residue was purified by silica chromatography using 0-100% ethyl acetate in cyclohexane over 80 mins. Pure fractions were evaporated to give the title compound (110 mg).
Reaction SMILES: CO[C:3]1([O:14]C)[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](=[O:13])[CH:5]=[CH:4]1.[C:16]1([CH3:34])[CH:21]=[CH:20][C:19]([S:22]([N:25]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:27]=[CH:26]2)(=[O:24])=[O:23])=[CH:18][CH:17]=1>>[OH:14][C:3]1([C:26]2[N:25]([S:22]([C:19]3[CH:20]=[CH:21][C:16]([CH3:34])=[CH:17][CH:18]=3)(=[O:24])=[O:23])[C:33]3[C:28]([CH:27]=2)=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](=[O:13])[CH:5]=[CH:4]1
Reactant: Cc1ccc(S(=O)(=O)n2ccc3ccccc32)cc1
Reactant: COC1(OC)C=CC(=O)c2ccccc21
Product: Cc1ccc(S(=O)(=O)n2c(C3(O)C=CC(=O)c4ccccc43)cc3ccccc32)cc1
Yield: 23 %

Procedure:
The title compound was prepared from 4,4-dimethoxy-4H-naphthalen-1-one and 1-(toluene4-sulfonyl)-1H-indole, according to Method E, described above. Yield 23%; mp 110-112° C.; 1H NMR (CDCl3) δ 8.35-8.39 (dd, J=8 Hz, 1H), 8.04 (d, J=8 Hz,1H), 7.74-7.97 (m, 6H), 7.32-7.48 (m, 6H), 6.53 (d, J=10 Hz,1H), 2.52 (s, 3H); 13C NMR (CDCl3) δ 189.7, 154.0, 150.2, 149.8, 148.8, 143.6, 140.1, 137.9, 135.7, 134.8, 133.6, 132.3, 131.7, 131.3, 130.7, 129.3, 126.6, 120.4, 120.3, 74.8, 26.6; MS (AP+) m/z 430.09 (M++1), 412.14.