Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH2:12][C:13]1[CH2:14][N:15]([CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([N+:27]([O-])=O)=[CH:23][CH:22]=2)[CH2:16][CH2:17][CH:18]=1>Cl.[Fe]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH2:12][C:13]1[CH2:14][N:15]([CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([NH2:27])=[CH:23][CH:22]=2)[CH2:16][CH2:17][CH:18]=1
Reactant: COc1ccc2[nH]cc(CC3=CCCN(CCc4ccc([N+](=O)[O-])cc4)C3)c2c1
Agent: [Fe]
Agent: Cl
Product: COc1ccc2[nH]cc(CC3=CCCN(CCc4ccc(N)cc4)C3)c2c1
Temperature: 25 °C

Procedure:
Iron powder (0.97 g; 0.0174) was added to a suspension of the compound of Description 8 [5-methoxy-3-[N-(2-(4-nitro-phenyl)-ethyl)-1,2,5,6-tetrahydro-pyridin-3-ylmethyl]-1H-indole] (1.36 g; 0.0035 mol) in 10% aqueous hydrochloric acid (70 ml). The reaction mixture was refluxed for 3 hours. The reaction mixture was then cool down to room temperature and quenched with a saturated solution of aqueous sodium carbonate. The resulting mixture was filtered through diatomaceous earth (Celite(R)), washed with water and extracted with methylene chloride. The organic extract was dried (MgSO4) and evaporated under vacuum. After purification by Flash Chromatography on silica gel using as eluent methylene chloride/methanol/ammonia (95/5/0.5), the title compound was obtained as a yellow solid (0.2 g).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]CCCC.[NH2:13][C:14]1[N:19]=[CH:18][CH:17]=[CH:16][N:15]=1>C1COCC1.C1(C)C=CC=CC=1>[C:2]1([C:16]2[CH:17]=[CH:18][N:19]=[C:14]([NH2:13])[N:15]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Brc1ccccc1
Reactant: Nc1ncccn1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: Nc1nccc(-c2ccccc2)n1
Temperature: -78 °C
Reaction time: 2 h
Yield: 9.7 %

Procedure:
To a solution of bromobenzene (4.43 mL, 42.06 mmol) in dry THF (100 mL) at −78° C. was added BuLi (394 mL, 63.08 mmol) and the mixture left to stir at −78° C. for 2 h. To this was added 2-aminopyrimidine (2.0 g, 21.03 mmol) in hot toluene (80 mL) over a 15 minutes period. The mixture was refluxed for 16 h and allowed to cool to room temperature and carefully quenched with aqueous NaHCO3. The mixture was filtered and the filtrate concentrated under vacuum. The residue was then dissolved in DCM and washed with aqueous NaHCO3, brine and dried (MgSO4). The solvent was removed to afford 350 mg of 47 (10%) as a pale yellow solid: 1H NMR (400 MHz, CDCl3) δ 8.32 (d, J=4.8 Hz, 1H), 7.97 (m, 2H), 7.45 (m, 3H), 7.02 (J=4.8 Hz, 1H). 5.27 (br s, 2H); MS (+)-ES [M+H]+ 172.2 m/z.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][C:6](=[O:13])/[C:5]/2=[CH:14]/OC.[CH3:17][N:18]([CH3:29])[CH2:19][CH2:20][S:21][C:22]1[CH:27]=[CH:26][C:25]([NH2:28])=[CH:24][CH:23]=1.C(N(CC)CC)C>CN(C)C=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][C:6](=[O:13])/[C:5]/2=[CH:14]\[NH:28][C:25]1[CH:24]=[CH:23][C:22]([S:21][CH2:20][CH2:19][N:18]([CH3:29])[CH3:17])=[CH:27][CH:26]=1
Reactant: CO/C=C1/C(=O)NC(=O)c2ccc(Br)cc21
Reactant: CN(C)CCSc1ccc(N)cc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CN(C)CCSc1ccc(N/C=C2\C(=O)NC(=O)c3ccc(Br)cc32)cc1
Reaction time: 0.17 h
Yield: 0.1 %

Procedure:
(4E)-6-Bromo-4-(methoxymethylene)isoquinoline-1,3(2H,4H)-dione (0.21 g, 0.76 mmol) and 4-(2-dimethylamino-ethylsulfanyl)-phenylamine (0.15 g, 0.76 mmol) were stirred in N,N-dimethylformamide (5 mL) and triethylamine (0.3 mL) at 60-70° C. for 5 minutes and then at room temperature for 10 minutes. The reaction mixture is quenched by the addition of water. The solid material is then collected, washed with diethyl ether, water, and methanol, and then dried under vacuum to give (4Z)-6-bromo-4-{[(4-{[2-(dimethylamino)ethyl]thio}phenyl)amino]methylene}isoquinoline-1,3(2H,4H)-dione (0.22 mg, 65%) as a golden powder.
Reaction SMILES: [C:1]([C:3]1[NH:7][C:6]([C:8]2[CH:13]=[CH:12][C:11]([NH:14][S:15]([CH2:18][CH3:19])(=[O:17])=[O:16])=[CH:10][CH:9]=2)=[CH:5][CH:4]=1)#[N:2].CC(C)([O-])C.[K+].[CH2:26](I)[CH2:27][CH2:28][CH3:29]>>[CH2:26]([N:7]1[C:3]([C:1]#[N:2])=[CH:4][CH:5]=[C:6]1[C:8]1[CH:9]=[CH:10][C:11]([NH:14][S:15]([CH2:18][CH3:19])(=[O:17])=[O:16])=[CH:12][CH:13]=1)[CH2:27][CH2:28][CH3:29]
Reactant: CCCCI
Reactant: CCS(=O)(=O)Nc1ccc(-c2ccc(C#N)[nH]2)cc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Product: CCCCn1c(C#N)ccc1-c1ccc(NS(=O)(=O)CC)cc1
Yield: 60.3 %

Procedure:
N-[4-(5-cyano-1H-pyrrol-2-yl)phenyl]ethanesulfonamide (0.150 g, 0.54 mmol) was alkylated according to the procedure of Example 40 using potassium tert-butoxide (1.08 mL of a 1M solution, 1.08 mmol) and butyl iodide (0.066 mL, 0.50 mmol) to afford the title compound (0.10 g, 6%).
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]2[CH:9]=[C:10]([NH:14][S:15]([C:18]3[CH:23]=[CH:22][C:21]([O:24]C)=[CH:20][C:19]=3[O:26]C)(=[O:17])=[O:16])[CH:11]=[CH:12][CH:13]=2)=[C:6]([NH:28][C@H:29]([C:31]2[N:36]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[C:35](=[O:43])[C:34]3=[C:44]([CH3:47])[CH:45]=[CH:46][N:33]3[N:32]=2)[CH3:30])[N:5]=[CH:4][N:3]=1.B(Br)(Br)Br>ClCCl>[NH2:1][C:2]1[C:7]([C:8]2[CH:9]=[C:10]([NH:14][S:15]([C:18]3[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][C:19]=3[OH:26])(=[O:17])=[O:16])[CH:11]=[CH:12][CH:13]=2)=[C:6]([NH:28][C@H:29]([C:31]2[N:36]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[C:35](=[O:43])[C:34]3=[C:44]([CH3:47])[CH:45]=[CH:46][N:33]3[N:32]=2)[CH3:30])[N:5]=[CH:4][N:3]=1
Reactant: COc1ccc(S(=O)(=O)Nc2cccc(-c3c(N)ncnc3N[C@@H](C)c3nn4ccc(C)c4c(=O)n3-c3ccccc3)c2)c(OC)c1
Agent: BrB(Br)Br
Solvent: ClCCl
Product: Cc1ccn2nc([C@H](C)Nc3ncnc(N)c3-c3cccc(NS(=O)(=O)c4ccc(O)cc4O)c3)n(-c3ccccc3)c(=O)c12
Yield: 55 %

Procedure:
(S)—N-(3-(4-Amino-6-((1-(5-methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)amino)pyrimidin-5-yl)phenyl)-2,4-dimethoxybenzenesulfonamide (108 mg, 0.17 mmol) was treated with boron tribromide (1M in dichloromethane, 0.90 ml, 0.9 mmol) with dichloromethane (20 ml) as a solvent at 100° C. for 2 h under microwave conditions. After evaporation of the solvent and usual workup with ethyl acetate and water, the residue was purified by reverse phase chromatography using SP1® Purification System to give 48 mg (55% yield) as a solid. Purity 99%.
Reaction SMILES: [CH2:1]([O:3][C:4]([C@@H:6]1[CH2:10][C:9](=[O:11])[CH2:8][C@H:7]1[C:12]([O:14]CC)=[O:13])=[O:5])[CH3:2].[Mg].[OH-].[Na+].ClCCl>O1CCN(CCS(O)(=O)=O)CC1>[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:10][C:9](=[O:11])[CH2:8][C@H:7]1[C:12]([OH:14])=[O:13])=[O:5])[CH3:2]
Reactant: CCOC(=O)[C@@H]1CC(=O)C[C@H]1C(=O)OCC
Agent: O=S(=O)(O)CCN1CCOCC1
Agent: [Mg]
Agent: [Na+]
Solvent: ClCCl
Product: CCOC(=O)[C@@H]1CC(=O)C[C@H]1C(=O)O
Yield: 46 %

Procedure:
60.44 g of rac-trans-4-oxo-cyclopentane-1,2-dicarboxylic acid diethyl ester (prepared according to E. Lee-Ruff et al., J. Org. Chem. 59, 2114, 1994 or J. Mittendorf et al., Synthesis, 136, 2003) was emulsified under vigorous stirring in 1.16 L 5 mM 2-morpholinoethanesulfonic acid, 50 mM magnesium acetetate buffer pH 6.2. 1.94 ml CALB L (liquid enzyme formulation from Novozymes, Denmark) was added and the pH kept constant at 6.2 under vigorous stirring by the automated addition (pH-stat) of 1.0 M NaOH-solution. After reaching 45% conversion (ca. 42 h reaction time; enantiomeric excess of formed acid still >95% according to GC in process control) 1.0 L dichloromethane was added. The aqueous phase was washed with 3×1.5 L dichloromethane, set to pH 3.0 using 85% phosphoric acid and extracted with 4×1.0 L ethyl acetate. The combined ethyl acetate phases were dried over sodium sulfate, evaporated and dried under high vacuum overnight to give 24.40 g of the title compound as white crystals: MS: 199.1 (M−H); >99% GC; [α]589 (20° C.)=−101.2° (c 1.0; EtOH); chiral GC: 95% ee [BGB-176, 30 m×0.25 mm; H2; 100° C. to 200° C. with 2° C./min].
Reaction SMILES: [C:1]([CH:4]([CH:6]1[C:18]2[N:17]3[CH:19]=[CH:20][N:21]=[C:16]3[C:15](=[O:22])[NH:14][C:13]=2[C:12]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]1=2)[OH:5])([OH:3])=[O:2].[CH3:23][NH:24][C:25](=[O:44])[NH:26]C1C=CC2C3NC(=O)C4N(C=CN=4)C=3CC=2C=1.O.C(O)(=O)C=O.[H-].[Na+].Cl>O.CS(C)=O>[C:1]([CH:4]([CH:6]1[C:18]2[N:17]3[CH:19]=[CH:20][N:21]=[C:16]3[C:15](=[O:22])[NH:14][C:13]=2[C:12]2[CH:11]=[CH:10][C:9]([NH:26][C:25]([NH:24][CH3:23])=[O:44])=[CH:8][C:7]1=2)[OH:5])([OH:3])=[O:2]
Reactant: CNC(=O)Nc1ccc2c(c1)Cc1c-2[nH]c(=O)c2nccn12
Reactant: O=C(O)C(O)C1c2ccccc2-c2[nH]c(=O)c3nccn3c21
Agent: Cl
Agent: O=CC(=O)O
Agent: [H-]
Solvent: O
Solvent: CS(C)=O
Product: CNC(=O)Nc1ccc2c(c1)C(C(O)C(=O)O)c1c-2[nH]c(=O)c2nccn12

Procedure:
The process is performed as in Example 15 for the preparation of 10-(1-carboxy-1-hydroxymethyl)-5H, 10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one but starting with 2 g of 8-(3-methylureido)-5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one, 32 ml of dimethyl sulphoxide, 0.93 g of glyoxylic acid monohydrate and 1.11 g of sodium hydride. After treatment of the reaction mixture with acetic acid (2.4 ml), the suspension is filtered and 100 ml of acetone are added to the filtrate. The greyish precipitate formed is filtered off, triturated with ethanol (2×50 ml), filtered off and dried at 60° C. under vacuum (1 mmHg; 0.13 kPa). The solid obtained (2.29 g) is treated with 24 ml of water and 12 ml of 1N hydrochloric acid. A brown precipitate forms which is filtered off, washed with water (2×5 ml), then with acetone (2×5 ml) and dried at 60° C. under vacuum (1 mmHg; 0.13 kPa). 1 g of 10-(1-carboxy-1-hydroxymethyl)-8-(3-methylureido)-5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one is obtained in the form of a dark yellow solid melting above 260° C. (Analysis, % calculated C: 55.28, H: 4.09, N: 18.96, O: 21.66, % found C: 55.1, H: 3.6, N: 18.9).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=3)[CH:13]=2)[N:8]([C:27]2[CH:32]=[CH:31][C:30]([N:33]([CH2:36][CH3:37])[CH2:34][CH3:35])=[CH:29][CH:28]=2)[C:7]=1[CH2:38][C:39]([O:41]CC)=[O:40])=[O:5])[CH3:2].[OH-].[Na+]>O1CCOCC1>[CH2:1]([O:3][C:4]([C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][C:16]3[CH:17]=[CH:18][C:19]([O:22][C:23]([F:26])([F:24])[F:25])=[CH:20][CH:21]=3)[CH:13]=2)[N:8]([C:27]2[CH:28]=[CH:29][C:30]([N:33]([CH2:36][CH3:37])[CH2:34][CH3:35])=[CH:31][CH:32]=2)[C:7]=1[CH2:38][C:39]([OH:41])=[O:40])=[O:5])[CH3:2]
Reactant: CCOC(=O)Cc1c(C(=O)OCC)c2cc(Oc3ccc(OC(F)(F)F)cc3)ccc2n1-c1ccc(N(CC)CC)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: CCOC(=O)c1c(CC(=O)O)n(-c2ccc(N(CC)CC)cc2)c2ccc(Oc3ccc(OC(F)(F)F)cc3)cc12

Procedure:
1-(4-Diethylaminophenyl)-2-ethoxycarbonylmethyl-5-(4-trifluoromethoxyphenoxy)indole-3-carboxylic acid ethyl ester (150 mg, 0.25 mmol, see step (a) Example 75) was hydrolysed at 55° C. for 3 h with NaOH (aq, 2 M, 2 mL) and dioxane (2 mL). Work-up as described in step (d) Example 1 gave the title compound. Yield 110 mg (77%).
Reaction SMILES: C1([C:7](=[S:23](=[O:25])=[O:24])[CH2:8][CH2:9][CH2:10][O:11][C:12]2[CH:13]=[CH:14][CH:15]=[C:16]3[C:21]=2[NH:20][C:19](=[O:22])[CH2:18][CH2:17]3)C=CC=CC=1.Cl[C:27]1[C:28](=O)[C:29](C#N)=[C:30](C#N)[C:31](=O)[C:32]=1Cl>>[C:27]1([S:23]([CH2:7][CH2:8][CH2:9][CH2:10][O:11][C:12]2[CH:13]=[CH:14][CH:15]=[C:16]3[C:21]=2[NH:20][C:19](=[O:22])[CH:18]=[CH:17]3)(=[O:24])=[O:25])[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
Reactant: O=C1CCc2cccc(OCCCC(c3ccccc3)=S(=O)=O)c2N1
Reactant: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Product: O=c1ccc2cccc(OCCCCS(=O)(=O)c3ccccc3)c2[nH]1

Procedure:
Prepared analogous to Example 86 from 8-(4-phenyl-sulfonyl-butoxy)-3,4-dihydro-carbostyril and 2,3-dichloro-5,6-dicyano-benzoquinone.
Reaction SMILES: C([BH3-])#N.[Na+].[Cl:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12]1[CH:20]=[CH:19][CH:18]=[C:17]2[C:13]=1[CH:14]=[CH:15][NH:16]2.[OH-].[Na+]>FC(F)(F)C(O)=O.O>[Cl:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12]1[CH:20]=[CH:19][CH:18]=[C:17]2[C:13]=1[CH2:14][CH2:15][NH:16]2
Reactant: Clc1ccccc1-c1cccc2[nH]ccc12
Agent: [BH3-]C#N
Agent: [Na+]
Agent: [OH-]
Solvent: O=C(O)C(F)(F)F
Solvent: O
Product: Clc1ccccc1-c1cccc2c1CCN2
Temperature: 0 °C
Reaction time: 16 h

Procedure:
558 g of sodium cyanoborohydride are added in portions to a suspension of 960 mg of 4-(2-chlorophenyl)-1H-indole in 11 ml of trifluoroacetic acid cooled to 0° C. The reaction medium is stirred for 16 hours while allowing it to rise to ambient temperature and then the pH is brought to neutrality with a sodium hydroxide solution. The reaction mixture is diluted with 300 ml of water then extracted with ethyl acetate (2×250 ml). The organic phases are combined and then concentrated to dryness under reduced pressure. After purification of the residue by silica column chromatography, elution being carried out with a mixture of heptane and ethyl acetate (80/20), 395 mg of 4-(2-chlorophenyl)-2,3-dihydro-1H-indole are obtained in the form of a colorless viscous oil.
Reaction SMILES: [N+:1]([C:4]1[CH:10]=[C:9]([O:11][C:12]([F:15])([F:14])[F:13])[CH:8]=[CH:7][C:5]=1[NH2:6])([O-])=O.CCO.[Cl-].[NH4+]>[Zn].O>[F:13][C:12]([F:14])([F:15])[O:11][C:9]1[CH:10]=[C:4]([NH2:1])[C:5]([NH2:6])=[CH:7][CH:8]=1
Reactant: Nc1ccc(OC(F)(F)F)cc1[N+](=O)[O-]
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: CCO
Solvent: O
Product: Nc1ccc(OC(F)(F)F)cc1N
Temperature: 60 °C
Reaction time: 1 h

Procedure:
To a mixture of 2-nitro-4-(trifluoromethoxy)aniline (1.17 g) and EtOH (20 mL) were added ammonium chloride (565 mg) and water (5 mL), followed by further adding zinc powder (1.73 g) at 60° C., and heating and stirring at 60° C. for 1 hour. The reaction mixture was cooled to room temperature, filtered over Celite, and washed with EtOAc. This filtrate was washed with a saturated aqueous NaHCO3 solution and brine in this order, dried over MgSO4, and then concentrated under reduced pressure to obtain 4-(trifluoromethoxy)benzene-1,2-diamine.
Reaction SMILES: [CH:1]1[C:6]2=[C:7]3[C:15](=[CH:16][CH:17]=[C:5]2[CH:4]=[CH:3][CH:2]=1)[C:14]1[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=1)[NH:8]3.[Al+3].[Cl-].[Cl-].[Cl-].[F:22][C:23]1[CH:31]=[CH:30][C:26]([C:27](Cl)=[O:28])=[CH:25][CH:24]=1>C(Cl)Cl>[CH2:17]([CH:5]([CH2:4][CH2:3][CH2:2][CH3:1])[CH2:6][N:8]1[C:7]2[C:15](=[CH:16][C:17]([C:27]([C:26]3[CH:30]=[CH:31][C:23]([F:22])=[CH:24][CH:25]=3)=[O:28])=[C:5]3[CH:4]=[CH:3][CH:2]=[CH:1][C:6]3=2)[C:14]2[C:9]1=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH3:16]
Reactant: O=C(Cl)c1ccc(F)cc1
Reactant: c1ccc2c(c1)ccc1c3ccccc3[nH]c21
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CCCCC(CC)Cn1c2ccccc2c2cc(C(=O)c3ccc(F)cc3)c3ccccc3c21
Temperature: 25 °C
Reaction time: 4 h
Yield: 87.9 %

Procedure:
To 11H-benzo[a]carbazole (8.24 g, 25.0 mmol) in CH2Cl2 (80 ml) are added AlCl3 (3.33 g, 25.0 mmol) and 4-fluorobenzoyl chloride (4.04 g, 25.5 mmol) at 0° C. After stirring at room temperature for 4 hours, the reaction mixture is poured into ice-water. The crude product is extracted with CH2Cl2, and washed with water and brine. After drying over MgSO4 and concentration, the crude product is purified by column chromatography on silica gel eluting with a mixed solvent of CH2Cl2 and n-hexane (1:9) to obtain a yellow solid (4.96 g, 44%). The structure is confirmed by 1H-NMR spectrum (CDCl3). δ [ppm]: 0.82-0.91 (m), 1.18-1.47 (m), 2.21-2.30 (m), 4.67-4.78 (m), 7.16 (t), 7.30 (t), 7.50 (t), 7.55-7.59 (m), 7.63-7.67 (m), 7.96-8.00 (m), 8.05 (d), 8.31 (s), 8.51 (d), 8.63 (d); 19F-NMR spectrum (CDCl3). δ [ppm] −105.89.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([NH:9]/[C:10](=[C:17]2\[C:18](=[O:26])[NH:19][C:20]3[C:25]\2=[CH:24][CH:23]=[CH:22][CH:21]=3)/[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:6]=[CH:7][CH:8]=1)#[N:2].Cl.C([O-])(=O)C.[NH4+:32]>CO>[C:1]([C:3]1[CH:4]=[C:5]([NH:9]/[C:10](=[C:17]2\[C:18](=[O:26])[NH:19][C:20]3[C:25]\2=[CH:24][CH:23]=[CH:22][CH:21]=3)/[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:6]=[CH:7][CH:8]=1)(=[NH:32])[NH2:2]
Reactant: N#Cc1cccc(N/C(=C2\C(=O)Nc3ccccc32)c2ccccc2)c1
Reactant: [NH4+]
Agent: CC(=O)[O-]
Agent: Cl
Solvent: CO
Product: N=C(N)c1cccc(N/C(=C2\C(=O)Nc3ccccc32)c2ccccc2)c1

Procedure:
Prepared analogously to Example 62 from (Z)-3-[1-(3-cyanophenylamino)-1-phenyl-methylidene]-2-indolinone and methanolic hydrochloric acid in methanol and ammonium acetate.
Reaction SMILES: [NH2:1][CH:2]1[CH2:8][CH:7]2[N:9]([CH3:10])[CH:4]([CH2:5][CH2:6]2)[CH2:3]1.[C:11]1([C:17]2[O:18][C:19]3[C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=[CH:22][C:20]=3[N:21]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[CH3:10][N:9]1[CH:7]2[CH2:6][CH2:5][CH:4]1[CH2:3][CH:2]([NH:1][C:26]([C:25]1[C:19]3[O:18][C:17]([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=4)=[N:21][C:20]=3[CH:22]=[CH:23][CH:24]=1)=[O:27])[CH2:8]2
Reactant: O=C(O)c1cccc2nc(-c3ccccc3)oc12
Reactant: CN1C2CCC1CC(N)C2
Product: CN1C2CCC1CC(NC(=O)c1cccc3nc(-c4ccccc4)oc13)C2
Yield: 57 %

Procedure:
N-(8-Methyl-8-azabicyclo[3.2.1]oct-3-yl)-2-phenylbenzoxazole-7-carboxamide was prepared from 3-amino-8-methyl-8-azabicyclo[3.2.1]octane and 2-phenylbenzoxazole-7-carboxylic acid using conditions similar to those described for Step C in Example 7. This compound was obtained in 57% yield as a white solid: mp 164-166° C.; 1H NMR (300 MHz, CH3OD) δ 8.25 (dd, J=8.1, 1.8 Hz, 2H), 7.90 (dd, J=8.1, 1.2 Hz, 1H), 7.80 (d, J=7.5 Hz, 1H), 7.64-7.58 (m, 3H), 7.50 (t, J=7.8 Hz, 1H), 4.25 (t, J=5.0 Hz, 1H), 3.63 (br s, 2H), 2.63 (s, 3H), 2.53-2.35 (m, 6H), 2.22-2.17 (m, 2H); MS (ESI) m/z 362 [M+H]+.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20]C(=O)N(C)C)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[K+]>CO.[NH4+].[Cl-]>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([SH:20])=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CN(C)C(=O)Sc1c(Cl)ccc2c1CCN(C(=O)OC(C)(C)C)CC2
Agent: [Cl-]
Agent: [K+]
Agent: [NH4+]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCc2ccc(Cl)c(S)c2CC1
Temperature: 25 °C
Yield: 104.2 %

Procedure:
Dissolve 3-tert-butoxycarbonyl-7-chloro-6-dimethylcarbamoylthio-2,3,4,5-tetrahydro-1H-benzo[d]azepine (706 mg, 1.84 mmol) in methanol (20 mL). Add potassium hydroxide (3.5 g, 55 mmol) and heat the mixture at reflux for 3 h. Cool to ambient temperature. Pour reaction in saturated aqueous NH4Cl solution. Extract three times with EtOAc. Combine organic extracts, dry over Na2SO4 and concentrate in vacuo to obtain crude 3-tert-butoxycarbonyl-7-chloro-6-mercapto-2,3,4,5-tetrahydro-1H-benzo[d]azepine (602 mg, 100%). Dissolve 3-tert-butoxycarbonyl-7-chloro-6-mercapto-2,3,4,5-tetrahydro-1H-benzo[d]azepine (282 mg, 0.9 mmol) in acetone (30 mL). Add 4-benzyloxybenzyl chloride (251 mg, 1.08 mmol), potassium carbonate (powder) (373 mg, 2.7 mmol) and potassium iodide (powder) (15 mg, 0.1 mmol) and reflux for 16 h. Cool the reaction to ambient temperature, dilute with acetone, filter and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (1:0 and 17:3) to give 6-(4-benzyloxybenzylthio)-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (309 mg, 67%). MS (ES+) m/z: 510 (M+H)+.
Reaction SMILES: [NH2:1][CH2:2][CH:3]([C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1)[CH:4]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:5](OCC)=[O:6].C(O)C>C1(C)C=CC=CC=1>[Cl:22][C:19]1[CH:20]=[CH:21][C:16]([CH:3]2[CH2:2][NH:1][C:5](=[O:6])[CH:4]2[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:17][CH:18]=1
Reactant: CCOC(=O)C(c1ccccc1)C(CN)c1ccc(Cl)cc1
Solvent: Cc1ccccc1
Solvent: CCO
Product: O=C1NCC(c2ccc(Cl)cc2)C1c1ccccc1

Procedure:
30 g. of ethyl 4-amino-3-p-chlorophenyl-2-phenyl-butyrate are heated for 15 minutes at 150°C. Liberation of ethanol is observed. The reaction medium is taken up in 120 ml. of toluene and the resulting solution is filered. After cooling the solution, the crystals formed are separated and recrystallized several times from toluene. 12 g. of 4-p-chlorophenyl-3-phenyl-2-pyrrolidinone are obtained; m.p. 148°-151°C. Nuclear magnetic resonance analysis shows that it is the cis-isomer.
Reaction SMILES: [C:1]([O:20]C(C)C)(=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9]CCCCCCCCC.[CH2:24](O)CCCCCCCCCCCCCCCCC>>[CH3:24][C@@H:1]([OH:20])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: CCCCCCCCCCCCCCCCCCO
Reactant: CCCCCCCCCCCCCCCCCC(=O)OC(C)C
Product: CCCCCCCC[C@@H](C)O
Reaction time: 48 h
Yield: 72 %

Procedure:
To the distillation residue, i.e., a mixture of (R)-(-)-2-decanol stearic acid ester and unreacted isopropyl stearate, were added 90 g of stearyl alcohol and 3 g Lipase PL. After regulating the particle size of the enzyme by ultrasonication in the same manner as described above, interesterification was carried out at 85° C. for 48 hours. The reaction mixture was subjected to simple distillation at 90° C. and 3 mmHg to recover highly pure free (R)-(-)-2-decanol (yield: 72%; chemical purity: 99.6%; optical purity: 84% ee).
Reaction SMILES: [O:1]1[C@H:3]2[CH2:4][C@H:5]3[C@:18]([CH3:20])([CH2:19][C@@H:2]12)[C@@H:17]1[C@H:8]([C@H:9]2[C@@:13]([CH2:15][C:16]1=[O:21])([CH3:14])[C@@H:12]([C:22]([O:24][CH3:25])=[O:23])[CH2:11][CH2:10]2)[CH2:7][CH2:6]3.[CH3:26][OH:27].S(=O)(=O)(O)O>O>[OH:1][C@@H:3]1[C@@H:2]([O:27][CH3:26])[CH2:19][C@@:18]2([CH3:20])[C@@H:5]([CH2:6][CH2:7][C@@H:8]3[C@@H:17]2[C:16](=[O:21])[CH2:15][C@@:13]2([CH3:14])[C@H:9]3[CH2:10][CH2:11][C@@H:12]2[C:22]([O:24][CH3:25])=[O:23])[CH2:4]1
Reactant: CO
Reactant: COC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@@H]5O[C@@H]5C[C@]4(C)[C@H]3C(=O)C[C@]12C
Agent: O=S(=O)(O)O
Solvent: O
Product: COC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](O)[C@@H](OC)C[C@]4(C)[C@H]3C(=O)C[C@]12C

Procedure:
2α,3α-Epoxy-17β-methoxycarbonyl-5α-androstan-11-one (500 mg.) in warm dry methanol (30 ml.) was treated with concentrated sulphuric acid (0.15 ml.). After 30 minutes the solution was poured into stirred water. The precipitated product was isolated, washed with water and dried over sodium hydroxide in vacuo to give fairly pure title compound (420 mg.) as a white powder; m.p. 170°-182°; [α]D + 68°,
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)[C:3]=1[NH2:16].[Cl:17][C:18]1[CH:26]=[CH:25][C:21]([C:22](Cl)=[O:23])=[C:20]([F:27])[CH:19]=1>N1C=CC=CC=1.C(O)C>[Cl:17][C:18]1[CH:26]=[CH:25][C:21]([C:22]([NH:16][C:3]2[C:2]([Cl:1])=[N:7][CH:6]=[N:5][C:4]=2[NH:8][C:9]2[CH:10]=[CH:11][C:12]([Cl:15])=[CH:13][CH:14]=2)=[O:23])=[C:20]([F:27])[CH:19]=1
Reactant: O=C(Cl)c1ccc(Cl)cc1F
Reactant: Nc1c(Cl)ncnc1Nc1ccc(Cl)cc1
Solvent: c1ccncc1
Solvent: CCO
Product: O=C(Nc1c(Cl)ncnc1Nc1ccc(Cl)cc1)c1ccc(Cl)cc1F
Temperature: 25 °C

Procedure:
6-Chloro-N4-(4-chlorophenyl)-pyrimidine-4,5-diamine I-(1A-1)a (6.6 g, 26 mmol) in pyridine (30 ml) was cooled to 0° C. and to it was added 4-chloro-2-fluorobenzoyl chloride (5 g, 26 mmol). The reaction was then allowed to warm to ambient temperature overnight. The heterogeneous reaction was diluted with ethanol (50 ml) and the resulting solid collected by filtration. The solids were slurried in toluene, which was then removed under reduced pressure to remove residual ethanol. The solid was slurried in diethyl ether and then collected by filtration to give I-(7A-91)a (8.3 g, 78%): +ACPI MS (M+1) 409.0; 1H NMR (400 MHz, CD3OD) δ 10.60 (s, 1H), 10.10 (s, 1H), 9.19 (s, 1H), 8.74 (t, J=8.1 Hz, 1H), 8.46–8.40 (m, 3H), 8.28 (dd, J=8.7, 2.1 Hz, 1H), 8.20 (d, J=8.7 Hz, 2H).