Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(=O)CCCCCCCCC/C=C\CCCC.CS(C)=O.C(Cl)(=O)C(Cl)=O.[CH3:28][CH2:29][CH2:30][CH2:31][CH2:32]/[CH:33]=[CH:34]\[CH2:35][CH2:36][CH2:37][CH:38]([OH:49])[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH3:48].CCN(CC)CC>>[CH3:48][CH2:47][CH2:46][CH2:45][CH2:44]/[CH:43]=[CH:42]\[CH2:41][CH2:40][CH2:39][C:38](=[O:49])[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH3:28]
Reactant: CCCCC/C=C\CCCC(O)CCCCCCCCCC
Agent: CCCC/C=C\CCCCCCCCCC=O
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: CCCCC/C=C\CCCC(=O)CCCCCCCCCC
Yield: 90.3 %

Procedure:
According to the procedure for compound 6, DMSO (0.080 mL, 1.1 mmol), oxalyl chloride (0.060 mL, 0.67 mmol), alcohol 19 (0.19 g, 0.61 mmol), and Et3N (0.42 mL, 3.1 mmol) were reacted to yield 20 (0.17 g, 91% yield, 88% Z as determined by quantitative 13C-NMR) as a colorless oil; 1H NMR (CDCl3): δ 5.39 (1H, m), 5.31 (1H, m), 2.39 (2H, t, J=7.5 Hz), 2.38 (2H, t, J=7.6 Hz), 2.04 (2H, m), 1.99 (2H, m), 1.63 (2H, m), 1.56 (2H, m), 1.20-1.37 (20H, m), 0.88 (6H, m); 13C NMR (CDCl3): δ 211.4, 131.0, 128.7, 42.9, 42.1, 31.9, 31.5, 29.6, 29.5, 29.4 (2C), 29.3 (2C), 23.9, 22.7, 22.6, 14.1 (2C); HRMS (FAB): 309.3148, [C21H40O+H]+ requires 309.3157.
Reaction SMILES: C(O)[C:2]([NH2:7])([CH2:5]O)[CH2:3]O.Cl.[CH3:10][O:11][C:12]1[CH:13]=[C:14](CC(=O)C)[CH:15]=[CH:16][C:17]=1[O:18][CH3:19].C1([C@H](N)C)C=CC=CC=1>>[CH3:10][O:11][C:12]1[CH:13]=[C:14]([CH2:5][C@H:2]([NH2:7])[CH3:3])[CH:15]=[CH:16][C:17]=1[O:18][CH3:19]
Reactant: NC(CO)(CO)CO
Reactant: COc1ccc(CC(C)=O)cc1OC
Agent: C[C@@H](N)c1ccccc1
Agent: Cl
Product: COc1ccc(C[C@@H](C)N)cc1OC

Procedure:
Using 10 ml of the cell-free extract, the components were reacted in 100 ml of a reaction mixture comprising a 0.1 M Tris-hydrochloric acid buffer (pH 8.5) containing 0.5 g of 1-(3,4-dimethoxyphenyl)-2-propanone and 0.34 g of (R)-1-phenylethylamine at 30° C. for 24 hours. As a result, 0.36 g of (R)-(3,4-dimethoxyphenyl)-2-aminopropane was formed.
Reaction SMILES: [F:1][C:2]1[CH:9]=[C:8]([C:10]2[N:15]=[CH:14][CH:13]=[CH:12][N:11]=2)[CH:7]=[CH:6][C:3]=1[CH:4]=O.N1(C2C=C[C:24]([CH:25]=[O:26])=CC=2)C=CC=N1>>[F:1][C:2]1[CH:9]=[C:8]([C:10]2[N:15]=[CH:14][CH:13]=[CH:12][N:11]=2)[CH:7]=[CH:6][C:3]=1/[CH:4]=[CH:24]/[CH:25]=[O:26]
Reactant: O=Cc1ccc(-n2cccn2)cc1
Reactant: O=Cc1ccc(-c2ncccn2)cc1F
Product: O=C/C=C/c1ccc(-c2ncccn2)cc1F

Procedure:
The title compound was prepared by a procedure analogous to Reference Example 30 by substituting 2-fluoro-4-(2-pyrimidinyl)benzaldehyde (prepared as described in Reference Example 15) for the 4-(1H-pyrazol-1-yl)-benzaldehyde of Reference Example 30. MS 229 (M+H)+.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3[N:11]=[C:12]([C:21]4[CH:29]=[CH:28][C:24]([C:25](O)=[O:26])=[CH:23][CH:22]=4)[NH:13][C:14]=3[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)=[CH:9][C:4]=2[O:3][CH2:2]1.C(Cl)(=O)C([Cl:33])=O>ClCCl.CN(C)C=O>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3[N:11]=[C:12]([C:21]4[CH:29]=[CH:28][C:24]([C:25]([Cl:33])=[O:26])=[CH:23][CH:22]=4)[NH:13][C:14]=3[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)=[CH:9][C:4]=2[O:3][CH2:2]1
Reactant: O=C(O)c1ccc(-c2nc(-c3ccc4c(c3)OCO4)c(-c3ccccn3)[nH]2)cc1
Reactant: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=C(Cl)c1ccc(-c2nc(-c3ccc4c(c3)OCO4)c(-c3ccccn3)[nH]2)cc1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
4-(4-Benzo[1,3]dioxol-5-yl-5-pyridin-2-yl-1H-imidazol-2-yl)benzoic acid (prepared according to the method of Example 1) (379 mg; 0.98 mmol ) was suspended in dry dichloromethane (20 ml) and treated with oxalyl chloride (2 ml) and N,N-dimethylformamide (1 drop). This mixture was stirred at ambient temperature for 5 h then evaporated to dryness under reduced pressure to give the title compound as a yellow powder.
Reaction SMILES: [C:1]([CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH:14]([NH:16][CH2:17][CH:18]([OH:25])[C:19]2[N:20]=[C:21]([CH3:24])[S:22][CH:23]=2)[CH3:15])=[CH:9][CH:8]=1)(OC)=[O:2].[NH3:26]>CO.O>[NH2:26][C:1]([CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH:14]([NH:16][CH2:17][CH:18]([OH:25])[C:19]2[N:20]=[C:21]([CH3:24])[S:22][CH:23]=2)[CH3:15])=[CH:9][CH:8]=1)=[O:2]
Reactant: N
Reactant: COC(=O)COc1ccc(CC(C)NCC(O)c2csc(C)n2)cc1
Solvent: CO
Solvent: O
Product: Cc1nc(C(O)CNC(C)Cc2ccc(OCC(N)=O)cc2)cs1

Procedure:
1 g (0.0027 mol) of N-[2-(4-Carbomethoxymethoxyphenyl)-1-methylethyl]-2-hydroxy-2-(2-methyl-thiazol-4-yl)ethanamine is dissolved in 5 ml of methanol and stirred with 5 of concentrated ammonia at room temperature for 3 hours. The mixture is then diluted with water and extracted with methylene chloride. The extract is dried over sodium sulphate, concentrated and purified on a silica gel column using ethyl acetate/methanol =9:1 as eluant.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]=[CH:10]C2C=CC=CC=2)=[CH:4][C:3]=1[O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[CH2:24]([O:26][C:27]1[CH:32]=[CH:31][C:30]([SiH:33]([CH3:35])[CH3:34])=[CH:29][CH:28]=1)[CH3:25]>C(O)(C)C.[H+].[H+].Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl>[CH2:24]([O:26][C:27]1[CH:32]=[CH:31][C:30]([Si:33]([CH2:10][CH2:9][CH2:8][C:5]2[CH:6]=[CH:7][C:2]([F:1])=[C:3]([O:17][C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH:4]=2)([CH3:34])[CH3:35])=[CH:29][CH:28]=1)[CH3:25]
Reactant: Fc1ccc(CC=Cc2ccccc2)cc1Oc1ccccc1
Reactant: CCOc1ccc([SiH](C)C)cc1
Agent: Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl
Agent: [H+]
Solvent: CC(C)O
Product: CCOc1ccc([Si](C)(C)CCCc2ccc(F)c(Oc3ccccc3)c2)cc1
Yield: 81.4 %

Procedure:
A few drops of a 30% solution of hexachloroplatinic acid in isopropanol are added twice at 22° C. to a mixture of 2.98 mol of 4-fluoro-3-phenoxyphenylallylbenzene (98.9% pure, 687 g) and 3.24 mol of 4-ethoxyphenyl(dimethyl)silane (595 g, 97.9% pure). After an induction phase of 11/2 hours, spontaneous heating to 130° C. takes place. After stirring is continued for a short period, 259 g of forerun are distilled off in a high vacuum of 0.4-0.15 mbar, followed by 1003 g of product (98.7% pure by GC). This corresponds to a yield of 81.4% of theory.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][NH2:10])[CH:5]=[CH:6][CH:7]=1.[OH:11][C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=1)[CH:15]=O.[BH4-].[Na+].O>CO>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][NH:10][CH2:15][C:14]2[CH:17]=[CH:18][CH:19]=[C:12]([OH:11])[CH:13]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: NCCc1cccc(Cl)c1
Reactant: O=Cc1cccc(O)c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: Oc1cccc(CNCCc2cccc(Cl)c2)c1
Temperature: 25 °C
Reaction time: 15 h

Procedure:
Combine 2-(3-chlorophenyl)ethylamine (1.866 gm; 15.28 mmol) and 3-hydroxybenzaldehyde (1.567 gm; 10.07 mmol) in 40 mL of methanol and stir at room temperature for 20 min and treat with sodium borohydride (0.950 gm; 25.1 mmol) in one portion. Stir the mixture at room temperature. After 15 h, add water (10 mL), and remove the methanol by rotary evaporation. Add to this slurry water (25 mL) and dichloromethane (50 mL), separate the layers and extract the aqueous layer with dichloromethane (50 mL). Wash the combined organic layers with saturated brine (3×), dry over MgSO4, and concentrate to give the title compound.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]([OH:14])=O.[CH2:15]([O:17][C:18](=[O:36])[C@@H:19]([NH:26][S:27]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)(=[O:29])=[O:28])[CH2:20][NH:21][C:22](=[O:25])[CH2:23][NH2:24])[CH3:16].CN1CCOCC1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[CH2:15]([O:17][C:18](=[O:36])[C@@H:19]([NH:26][S:27]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)(=[O:28])=[O:29])[CH2:20][NH:21][C:22](=[O:25])[CH2:23][NH:24][C:12](=[O:14])[CH2:11][CH2:10][CH2:9][CH2:8][NH:7][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=1)[CH3:16]
Reactant: O=C(O)CCCCNc1ccccn1
Reactant: CCOC(=O)[C@H](CNC(=O)CN)NS(=O)(=O)c1ccccc1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN1CCOCC1
Solvent: CN(C)C=O
Product: CCOC(=O)[C@H](CNC(=O)CNC(=O)CCCCNc1ccccn1)NS(=O)(=O)c1ccccc1

Procedure:
Acid 3-3 (186 mg, 0.55 mmol), amine 3-6 (150 mg, 0.46 mmol), NMM (0.20 mL, 1.8 mmol) and BOP (302 mg, 0.68 mmol) were combined in 3 mL DMF. After 5 d the DMF was removed on a rotary evaporator, the residue was diluted with EtOAc, then washed with water, sat. NaHCO3, and brine, dried (MgSO4), filtered and concentrated. Flash chromatography (silica, 25% i-PrOH/EtOAc) provided 3-7 as a colorless oil.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[C:11]([CH:18]=[CH:19][CH:20]=1)[C:12]([O:14]CC#N)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:21]([O:28][C:29](=[O:32])[CH2:30][NH2:31])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.CC1C=CC(S(O)(=O)=O)=CC=1>CN(C)C1C=CN=CC=1.C(N(CC)CC)C>[CH2:21]([O:28][C:29](=[O:32])[CH2:30][NH:31][C:12](=[O:14])[C:11]1[CH:18]=[CH:19][CH:20]=[C:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH:10]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: CC(C)(C)OC(=O)Nc1cccc(C(=O)OCC#N)c1
Reactant: NCC(=O)OCc1ccccc1
Agent: CN(C)c1ccncc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)Nc1cccc(C(=O)NCC(=O)OCc2ccccc2)c1
Temperature: 80 °C
Yield: 18.8 %

Procedure:
Cyanomethyl 3-(t-butyloxycarbonylamino)-benzoate [compound of Example 61-(2)] (27.6 g), glycine benzyl ester·p-toluenesulfonate (33.7 g), triethylamine (20.2 g) and 4-dimethylaminopyridine (0.2 g) are mixed. The mixture is stirred at 80° C. two nights. The reaction mixture is extracted with ethyl acetate (200 ml). The extract is washed with water, and ethyl acetate is distilled off under reduced pressure. The residue is purified by a silica gel column chromatography (eluant, chloroform-ethyl acetate). The fractions containing the desired compound are collected, and the solvent is distilled off under reduced pressure. The residue is recrystallized from 70% aqueous acetonitrile to give N-[3-(t-butyloxycarbonylamino)benzoyl]glycine benzyl ester (7.2 g).
Reaction SMILES: C(Cl)(=O)C(Cl)=O.C(Cl)Cl.[C:10]([OH:29])(=O)[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]/[CH:18]=[CH:19]\[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27].[CH2:30]([NH:32][CH2:33][CH3:34])[CH3:31]>O>[CH2:30]([N:32]([CH2:33][CH3:34])[C:10](=[O:29])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]/[CH:18]=[CH:19]\[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[CH3:31]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Reactant: CCNCC
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: O
Product: CCCCCCCC/C=C\CCCCCCCC(=O)N(CC)CC
Temperature: 25 °C
Reaction time: 4 h
Yield: 81.5 %

Procedure:
In a nitrogen atmosphere, oxalyl chloride (0.46 mL, 5.4 mmol) was dropped into an absolute methylene chloride solution (8.5 mL) of oleic acid (503 mg, 1.8 mmol) under ice cooling. The solution was then stirred at room temperature for four hours. Thereafter it was concentrated under reduced pressure. Diethylamine (1.0 mL, 9.7 mmol) was added to the resultant residue, which was then stirred at room temperature for 0.5 hour. Water was then added, and extraction was performed with ethyl acetate. The organic layer thus obtained was washed with saturated saline, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The crude extract thus obtained was purified using column chromatography (n-hexane:ethyl acetate=1:2). Thus (Z)-N,N-diethyl-9-octadecenamide (495 mg, 82%) was obtained as a colorless oily matter.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:10]2[N:11]([CH3:16])[C:12]([SH:15])=[N:13][CH:14]=2)[OH:9])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:24][CH2:25][CH2:26][Cl:27]>CC(C)=O.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([C:10]2[N:11]([CH3:16])[C:12]([S:15][CH2:24][CH2:25][CH2:26][Cl:27])=[N:13][CH:14]=2)[OH:9])=[CH:6][CH:7]=1
Reactant: ClCCCBr
Reactant: Cn1c(C(O)c2ccc(Cl)cc2)cnc1S
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CC(C)=O
Product: Cn1c(C(O)c2ccc(Cl)cc2)cnc1SCCCCl
Temperature: 25 °C
Reaction time: 16 h
Yield: 68.4 %

Procedure:
The product of Example I, Step A (0.09 g) in acetone (2 mL) and DMF (2 mL) was treated with K2CO3 (0.2 g) followed by 1-bromo-3-chloropropane (0.11 g). The mixture was allowed to stir at rt for 16 h and was then partitioned between EtOAc (50 mL) and brine (50 mL). The organic layer was separated and washed with brine (2×200 mL), dried over Na2SO4, filtered, and evaporated to give the crude product. The crude product was purified by silica gel chromatography using 2-5% MeOH/CH2Cl2 as the eluent to provide (4-Chloro-phenyl)-[2-(3-chloro-propylsulfanyl)-3-methyl-3H-imidazol-4-yl]-methanol (0.08 g, 69%); M calc=330; M+H found=331.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:9]2[N:13]3[C:14]([CH3:18])=[CH:15][CH:16]=[CH:17][C:12]3=[N:11][C:10]=2[C:19](=O)[CH3:20])[CH:5]=[C:6]([F:8])[CH:7]=1.C([O-])(=O)C.[NH4+].C([BH3-])#[N:28].[Na+]>CO>[F:1][C:2]1[CH:3]=[C:4]([C:9]2[N:13]3[C:14]([CH3:18])=[CH:15][CH:16]=[CH:17][C:12]3=[N:11][C:10]=2[CH:19]([NH2:28])[CH3:20])[CH:5]=[C:6]([F:8])[CH:7]=1
Reactant: CC(=O)c1nc2cccc(C)n2c1-c1cc(F)cc(F)c1
Reactant: [BH3-]C#N
Agent: CC(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CO
Product: Cc1cccc2nc(C(C)N)c(-c3cc(F)cc(F)c3)n12
Temperature: 65 °C
Yield: 55.2 %

Procedure:
A solution of 1-[3-(3,5-difluorophenyl)-5-methylimidazo[1,2-a]pyridin-2-yl]ethanone (0.23 g, 0.82 mmol) in methanol (9.5 mL) was treated with ammonium acetate (0.63 g, 8.2 mmol) and heated at 65° C. for 1 h. The reaction mixture was treated with sodium cyanoborohydride (0.15 g, 2.5 mmol) and heated at 65° C. for 4 h. The reaction mixture was concentrated and purified by preparative LCMS to give the desired product (0.13 g, 56%) as a colorless oil. LCMS for C16H16F2N3 (M+H)+: m/z=288.1.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:23][C:24]2[CH:25]=[N:26][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:28][CH:29]=2)[CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]1[S:13][CH:14]([CH2:17][C:18]([O:20]CC)=[O:19])[CH2:15][N:16]=1)=[CH:8]2.[OH-].[Na+]>O1CCCC1.C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:23][C:24]2[CH:25]=[N:26][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:28][CH:29]=2)[CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]1[S:13][CH:14]([CH2:17][C:18]([OH:20])=[O:19])[CH2:15][N:16]=1)=[CH:8]2
Reactant: CCOC(=O)CC1CN=C(c2cc3cc(Oc4ccc(S(C)(=O)=O)nc4)cc(OC)c3[nH]2)S1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: COc1cc(Oc2ccc(S(C)(=O)=O)nc2)cc2cc(C3=NCC(CC(=O)O)S3)[nH]c12
Temperature: 25 °C
Reaction time: 1 h
Yield: 92.6 %

Procedure:
Ethyl [2-(7-methoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetate (11.06 g) was dissolved in a mixture of tetrahydrofuran (100 mL) and ethanol (100 mL). To the mixture was added 1M aqueous sodium hydroxide solution (37 mL) and the mixture was stirred at room temperature for 1 h. The mixture was concentrated under reduced pressure. The residue was dissolved in water and 1M hydrochloric acid (37 mL) was added to the mixture. The resulting yellow suspension was filtered to collect a yellow solid. The solid was dissolved in ethyl acetate-tetrahydrofuran. The solution was dried over magnesium sulfate, filtered and concentrated. The residual solid was washed with diethyl ether to give the title compound (9.65 g, 93%) as a yellow solid. MS 462 (MH+).
Reaction SMILES: [NH:1]1[C:5]2=[C:6]([NH:10][C:11](=[O:13])[CH3:12])[N:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2]1.[Cl:14][C:15]1[CH:20]=[C:19]([C:21](=[O:25])[NH:22][CH2:23][CH3:24])[CH:18]=[C:17]([Cl:26])[C:16]=1[C:27](Cl)=[O:28]>>[C:11]([NH:10][C:6]1[N:7]=[CH:8][CH:9]=[C:4]2[C:3]([C:27]([C:16]3[C:17]([Cl:26])=[CH:18][C:19]([C:21]([NH:22][CH2:23][CH3:24])=[O:25])=[CH:20][C:15]=3[Cl:14])=[O:28])=[CH:2][NH:1][C:5]=12)(=[O:13])[CH3:12]
Reactant: CC(=O)Nc1nccc2cc[nH]c12
Reactant: CCNC(=O)c1cc(Cl)c(C(=O)Cl)c(Cl)c1
Product: CCNC(=O)c1cc(Cl)c(C(=O)c2c[nH]c3c(NC(C)=O)nccc23)c(Cl)c1

Procedure:
4-{[7-(Acetylamino)-1H-pyrrolo[2,3-c]pyridin-3-yl]carbonyl}-3,5-dichloro-N-ethylbenzamide was prepared from N-(1H-pyrrolo[2,3-c]pyridin-7-yl) acetamide and 2,6-dichloro-4-(ethylcarbamoyl)benzene carbonyl chloride (Compound No. 9).
Reaction SMILES: Br[C:2]1[C:10]2[N:9]3[CH2:11][CH2:12][CH2:13][NH:14][C:15](=[O:16])[C:8]3=[CH:7][C:6]=2[CH:5]=[C:4]([C:17]#[N:18])[CH:3]=1.[F:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[C:24]([F:26])[CH:25]=1>>[F:19][C:20]1[CH:21]=[C:22]([C:2]2[C:10]3[N:9]4[CH2:11][CH2:12][CH2:13][NH:14][C:15](=[O:16])[C:8]4=[CH:7][C:6]=3[CH:5]=[C:4]([C:17]#[N:18])[CH:3]=2)[CH:23]=[C:24]([F:26])[CH:25]=1
Reactant: OB(O)c1cc(F)cc(F)c1
Reactant: N#Cc1cc(Br)c2c(c1)cc1n2CCCNC1=O
Product: N#Cc1cc(-c2cc(F)cc(F)c2)c2c(c1)cc1n2CCCNC1=O

Procedure:
The title compound, light grey solid (65 mg, 77%), MS (ISP) m/z=338.6 [(M+H)+], mp 211° C., was prepared in accordance with the general method of example 1 from 7-bromo-1-oxo-2,3,4,5-tetrahydro-[1,4]diazepino[1,2-a]indole-9-carbonitrile (intermediate 20) (76.0 mg, 0.25 mmol) and commercially available 3,5-difluoro-phenylboronic acid (51.3 mg, 0.325 mmol).
Reaction SMILES: [NH2:1][CH:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3]1.[C:11](Cl)(=[O:19])[CH2:12][CH2:13][CH2:14][CH2:15][C:16](Cl)=[O:17]>CCOCC>[CH:2]1([NH:1][C:11](=[O:19])[CH2:12][CH2:13][CH2:14][CH2:15][C:16]([NH:1][CH:2]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH2:4][CH2:3]2)=[O:17])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3]1
Reactant: O=C(Cl)CCCCC(=O)Cl
Reactant: NC1CCc2ccccc21
Solvent: CCOCC
Product: O=C(CCCCC(=O)NC1CCc2ccccc21)NC1CCc2ccccc21
Reaction time: 0.75 h
Yield: 60 %

Procedure:
Racemic 1-aminoindan (5.7 g, 43 mmole) in ether (20 ml) stirred in ice, was treated dropwise with adipoyl chloride (1.83 g, 10 mmole) in ether (10 ml). After 30 min. the solid was filtered and slurried with water for 45 min. The insoluble solid was collected, air dried (2.82 g) and crystallized from HOAc/H2O, washed with acetic acid/water (1:1), ethanol and ether and then dried to give 2.26 g (60% title compound. Melting point: 227° C.
Reaction SMILES: [CH3:1][NH2:2].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][C:13]2[N:16]=[C:17]([NH:19][C:20]([O:22]C3C=CC=CC=3)=O)[S:18][C:12]=2[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]>CN(C=O)C.O>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][C:13]2[N:16]=[C:17]([NH:19][C:20]([NH:2][CH3:1])=[O:22])[S:18][C:12]=2[CH2:11]1)=[O:9])([CH3:4])([CH3:5])[CH3:6]
Reactant: CC(C)(C)OC(=O)N1CCc2nc(NC(=O)Oc3ccccc3)sc2C1
Reactant: CN
Solvent: CN(C)C=O
Solvent: O
Product: CNC(=O)Nc1nc2c(s1)CN(C(=O)OC(C)(C)C)CC2
Temperature: 25 °C
Reaction time: 12 h
Yield: 90.7 %

Procedure:
25 mg methylamine was added to 200 mg 2-phenoxycarbonylamino-6,7-dihydro-4H-thiazolo-[5,4-c]pyridine-5-carboxylic acid tert-butyl ester in 25 mL DMF. The reaction was stirred for 12 h at RT, diluted with water and extracted with ethyl acetate. The organic layer was washed with brine solution and concentrated. The residue was purified by column chromatographie (silica gel, eluent: 40% ethylacetate in hexane) to give 151 mg of desired product. (M+H)+: 313
Reaction SMILES: C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1.[Si:13]([O:20][CH2:21]/[CH:22]=[N:23]/[S@:24]([C:26]([CH3:29])([CH3:28])[CH3:27])=[O:25])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]>C1(C)C=CC=CC=1.[Cl-].[Na+].O>[Si:13]([O:20][CH2:21][C@@H:22]([NH:23][S@:24]([C:26]([CH3:29])([CH3:28])[CH3:27])=[O:25])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]
Reactant: CC(C)(C)[S@](=O)/N=C/CO[Si](C)(C)C(C)(C)C
Reactant: Brc1ccccn1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Product: CC(C)(C)[S@](=O)N[C@H](CO[Si](C)(C)C(C)(C)C)c1ccccn1
Yield: 46.4 %

Procedure:
To a solution of toluene (40 mL) cooled to −78° C. was added butyl lithium (1.6 M in hexanes, 5.57 mL, 13.9 mmol) at a rate such that the internal temperature did not exceed −50° C., and the reaction stirred until the internal temperature returned to −78° C. 2-Bromopyridine (1.20 mL, 12.7 mmol) in toluene (4 mL) was added to the reaction mixture at a rate such that the temperature did not exceed −65° C. The reaction was stirred at −78° C. for 1 hour. To the reaction was added (S,E)-N-(2-(tert-butyldimethylsilyloxy)ethylidene)-2-methylpropane-2-sulfinamide (3.58 g, 13.9 mmol) in toluene (20 mL) at a rate such that the internal temperature did not exceed −60° C. The reaction was stirred at −78° C. for 2 hours. To the −78° C. solution was added brine (50 mL) and the mixture was partitioned between EtOAc/water (300 mL total). The organic layer was washed with brine (50 mL), dried over MgSO4 and concentrated in vacuo. The crude material was chromatographed using 40% EtOAc/DCM as eluent to yield (S)—N—((S)-2-(tert-butyldimethylsilyloxy)-1-(pyridin-2-yl)ethyl)-2-methylpropane-2-sulfinamide (2.1 g, 46.7%).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[C:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])=[CH:15][CH:14]=2)=[O:11])=[CH:4][CH:3]=1.[Cl:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC(N=NC(OCC)=O)=O)C>O1CCCC1.C1(C)C=CC=CC=1>[Cl:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][O:1][C:2]1[CH:3]=[CH:4][C:5](/[CH:8]=[CH:9]/[C:10]([O:12][C:13]2[CH:14]=[CH:15][C:16]([O:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])=[CH:17][CH:18]=2)=[O:11])=[CH:6][CH:7]=1
Reactant: CCCCCOc1ccc(OC(=O)/C=C/c2ccc(O)cc2)cc1
Reactant: OCCCCCCCl
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CCCCCOc1ccc(OC(=O)/C=C/c2ccc(OCCCCCCCl)cc2)cc1
Temperature: 0 °C
Reaction time: 0.42 h
Yield: 74.9 %

Procedure:
7.35 g (22.5 mmol) 4-pentoxyphenyl (2E)-3-{4-hydroxyphenyl}acrylate, 3.36 g (24.6 mmol) 6-chloro-1-hexanol and 6.45 g (24.6 mmol) of triphenylphosphine were dissolved in 100 ml of tetrahydrofurane. The colourless solution was subsequently cooled to 0° C. and 4.28 g (24.6 mmol) of a 40% solution of azodicarboxylic acid diethyl ester in toluene were added dropwise thereto over a period of 25 minutes. The mixture was subsequently allowed to react for 4 h at 0° C. The reaction mixture was reduced in volume by evaporation. The resulting residue was added to a mixture of methanol and water (3:2) and was then extracted with a mixture of tert.-butyl-methylether:hexane 1:1. The tert.-butyl-methylether:hexane phase was washed repeatedly with water, dried over magnesium sulphate, filtered and concentrated by rotary evaporation to yield 7.5 g 4-pentoxyphenyl (2E)-3-{4-(6-chlorohexyloxy)phenyl}acrylate as yellowish crystals.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([NH:10]N=C2CCCNC2=O)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[CH:19]([OH:21])=O>O>[F:1][C:2]1[CH:3]=[C:4]2[C:5]([C:2]3[CH2:3][CH2:4][NH:10][C:19](=[O:21])[C:7]=3[NH:10]2)=[CH:6][C:7]=1[O:8][CH3:9]
Reactant: O=CO
Reactant: COc1ccc(NN=C2CCCNC2=O)cc1F
Solvent: O
Product: COc1cc2c3c([nH]c2cc1F)C(=O)NCC3
Temperature: 100 °C
Reaction time: 1 h

Procedure:
A mixture of 3-[(3-fluoro-4-methoxyphenyl)hydrazinylidene]piperidin-2-one (a mixture of E and Z isomers) (2.45 g) and formic acid (25.0 mL) was stirred at 100° C. for 1 hour. The reaction mixture was cooled to room temperature, and then water (40.0 mL) was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The insoluble materials were separated by filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform:methanol=10:0 to 10:1) to obtain 7-fluoro-6-methoxy-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-one (780 mg) as a brown solid.