Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:3]=1[C:4]([OH:6])=O.C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[NH2:25][CH:26]1[CH2:31][CH2:30][C:29](=[O:32])[NH:28][C:27]1=[O:33].C(=O)([O-])O.[Na+]>C(#N)C>[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:3]=1[C:4]([NH:25][CH:26]1[CH2:31][CH2:30][C:29](=[O:32])[NH:28][C:27]1=[O:33])=[O:6]
Reactant: NC1CCC(=O)NC1=O
Reactant: Cc1ccc(N)c(C(=O)O)c1
Agent: Cl
Agent: O=C([O-])O
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CC#N
Product: Cc1ccc(N)c(C(=O)NC2CCC(=O)NC2=O)c1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 69 %

Procedure:
A mixture of 2-amino-5-methylbenzoic acid (1.0 g, 6.6 mmol) and CDI (1.0 g, 6.1 mmol) in acetonitrile (15 mL) was stirred at room temperature for 1.5 hours. To the suspension, was added 3-amino-piperidine-2,6-dione hydrogen chloride (1.0 g, 6.1 mmol) and sodium hydrogen carbonate (0.45 g, 3.6 mmol), and the mixture was heated at 50° C. for 21 hours. The suspension was cooled to room temperature for 1 hour. The suspension was filtered and washed with acetonitrile (20 mL), water (2×20 mL) and ethyl acetate (20 mL) to give 2-amino-N-(2,6-dioxo-piperidin-3-yl)-5-methyl-benzamide as a blue solid (1.1 g, 63% yield): 1H NMR (DMSO-d6) δ 1.91-1.98 (m, 1H, CHH), 2.05-2.14 (m, 1H, CHH), 2.17 (s, 3H, CH3), 2.50-2.56 (m, 1H, CHH), 2.73-2.85 (m, 1H, CHH), 4.69-4.77 (m, 1H, NCH), 6.20 (br, 2H, NH2), 6.63 (d, J=9 Hz, 1H, Ar), 7.00 (dd, J=2, 8 Hz, 1H, Ar), 7.34 (d, J=2 Hz, 1H, Ar), 8.43 (d, J=8 Hz, 1H, NH), 10.84 (s, 111, NH); 13C NMR (DMSO-d6) δ 19.89, 24.13, 30.92, 48.93, 113.87, 116.48, 122.81, 127.87, 132.72, 147.40, 168.55, 172.40, 172.97.
Reaction SMILES: O.Cl.[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]=[CH:12][CH2:13][CH2:14][CH2:15][CH2:16][N:17]2[CH:21]=[CH:20][N:19]=[CH:18]2)=[CH:7][CH:6]=1.C(=O)(O)[O-].[Na+].[H][H]>C(O)C>[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][N:17]2[CH:21]=[CH:20][N:19]=[CH:18]2)=[CH:9][CH:10]=1
Reactant: [H][H]
Reactant: COc1ccc(C=CCCCCn2ccnc2)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: COc1ccc(CCCCCCn2ccnc2)cc1

Procedure:
Add 1 ml water to 400 mg of the compound prepared in Example 72, then add 100 mg sodium bicarbonate followed by 25 ml ethanol. Add 100 mg PtO and add hydrogen under 30 psi for 20 hr. Partition with water/methylene chloride. Elute on a silica column with 100% methylene chloride then 5% methanol/methylene chloride to yield the title compound.
Reaction SMILES: [CH3:1][N:2]([CH3:22])[C:3]1[CH:4]=[C:5]([CH:10]=[C:11]([N:19]([CH3:21])[CH3:20])[C:12]=1[N:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:6](OC)=[O:7].O1CCCC1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C(OCC)(=O)C>[CH3:1][N:2]([CH3:22])[C:3]1[CH:4]=[C:5]([CH:10]=[C:11]([N:19]([CH3:21])[CH3:20])[C:12]=1[N:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[CH2:6][OH:7]
Reactant: COC(=O)c1cc(N(C)C)c(N2CCCCC2)c(N(C)C)c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CN(C)c1cc(CO)cc(N(C)C)c1N1CCCCC1

Procedure:
A solution of 25 g. of methyl 3,5-bis(dimethylamino)-4-piperidinobenzoate in 150 ml. of absolute tetrahydrofuran was added dropwise to a solution of lithium aluminum hydride in 300 ml. of absolute tetrahydrofuran, and the mixture was boiled under reflux for 3 hours. After cooling, the excess lithium aluminum hydride was cautiously decomposed with 100 ml. of ethyl acetate and then with 3 ml. of water and the solution evaporated to dryness. The residue was taken up in water, the oily product extracted with ethyl acetate and the ethyl acetate solution dried and evaporated. After recrystallization from high-boiling petroleum ether, there was obtained 3,5-bis(dimethylamino)-4-piperidinobenzyl alcohol having a melting point of 90°-92° C.
Reaction SMILES: [OH:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([C:10](=[O:12])[CH3:11])=[CH:4][C:3]=1[O:13][CH3:14].[NH:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:17]([CH:24]=O)=[CH:16]1.N1CCCCC1>C(O)C>[OH:1][C:2]1[C:3]([O:13][CH3:14])=[CH:4][C:5]([C:10](=[O:12])/[CH:11]=[CH:24]/[C:17]2[C:18]3[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=3)[NH:15][CH:16]=2)=[CH:6][C:7]=1[O:8][CH3:9]
Reactant: O=Cc1c[nH]c2ccccc12
Reactant: COc1cc(C(C)=O)cc(OC)c1O
Solvent: C1CCNCC1
Solvent: CCO
Product: COc1cc(C(=O)/C=C/c2c[nH]c3ccccc23)cc(OC)c1O
Yield: 19.2 %

Procedure:
4'-Hydroxy-3',5'-dimethoxyacetophenone (1.96 g) and indole-3-carboxaldehyde (1.45 g) were dissolved in ethanol (20 ml), and piperidine (0.85 g) was added thereto, followed by heating under reflux for 32 hours. The reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography. The obtained crude crystals were recrystallized from ethyl acetate to give Compound 70 (0.62 g).
Reaction SMILES: Br[C:2]1[CH:17]=[N:16][C:5]2[NH:6][C:7]3[CH:12]=[N:11][C:10]([C:13]([OH:15])=[O:14])=[CH:9][C:8]=3[C:4]=2[CH:3]=1.[F:18][C:19]([F:30])([F:29])[C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=1.S(=O)(=O)(O)O>C(#N)C.C(=O)([O-])[O-].[Na+].[Na+].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:18][C:19]([F:30])([F:29])[C:20]1[CH:25]=[C:24]([C:2]2[CH:17]=[N:16][C:5]3[NH:6][C:7]4[CH:12]=[N:11][C:10]([C:13]([OH:15])=[O:14])=[CH:9][C:8]=4[C:4]=3[CH:3]=2)[CH:23]=[CH:22][CH:21]=1
Reactant: OB(O)c1cccc(C(F)(F)F)c1
Reactant: O=C(O)c1cc2c(cn1)[nH]c1ncc(Br)cc12
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: O=S(=O)(O)O
Solvent: CC#N
Product: O=C(O)c1cc2c(cn1)[nH]c1ncc(-c3cccc(C(F)(F)F)c3)cc12
Temperature: 140 °C

Procedure:
A degassed mixture of 3-bromo-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carboxylic acid (20.0 mg, 68.5 μmol), 3-(trifluoromethyl)phenylboronic acid (19.5 mg, 0.103 mmol), and bis(triphenylphosphine)palladium(II) dichloride (2.4 mg, 3.4 μmol) in acetonitrile (0.3 mL) and 2N aqueous sodium carbonate solution (0.3 mL) was heated under microwave irradiation at 140° C. for 10 minutes. The cooled reaction mixture was acidified with 10% aqueous sulfuric acid. The solid was removed by filtration and the resultant filtrate was purified by preparative HPLC (5-45% MeCN over 45 min, 35 mL/min) to afford the title compound. 1H NMR (DMSO-D6, 400 MHz): 12.75 (s, 1H), 9.38-9.00 (m, 3H), 8.21 (m, 1H), 7.78 (m, 2H), 7.65-7.60 (m, 2H). LCMS (Method D): RT=10.76 min, M+H+=358.
Reaction SMILES: [F:1][C:2]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:3]=1[CH2:4][N:5]1[C:9]2=[CH:10][N:11]=[C:12]([C:14]([OH:16])=O)[CH:13]=[C:8]2[C:7]([CH2:17][N:18]2[CH2:23][CH2:22][C@@H:21]3[C:24](=[O:27])[NH:25][CH2:26][C@@H:20]3[CH2:19]2)=[CH:6]1.Cl.[CH3:34][NH:35][OH:36]>>[F:1][C:2]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:3]=1[CH2:4][N:5]1[C:9]2=[CH:10][N:11]=[C:12]([C:14]([N:35]([OH:36])[CH3:34])=[O:16])[CH:13]=[C:8]2[C:7]([CH2:17][N:18]2[CH2:23][CH2:22][C@@H:21]3[C:24](=[O:27])[NH:25][CH2:26][C@@H:20]3[CH2:19]2)=[CH:6]1
Reactant: CNO
Reactant: O=C(O)c1cc2c(CN3CC[C@@H]4C(=O)NC[C@@H]4C3)cn(Cc3ccc(F)cc3F)c2cn1
Agent: Cl
Product: CN(O)C(=O)c1cc2c(CN3CC[C@@H]4C(=O)NC[C@@H]4C3)cn(Cc3ccc(F)cc3F)c2cn1

Procedure:
The title compound was prepared from rac-1-(2,4-difluorobenzyl)-3-{[(3aR*,7aS*)-1-oxooctahydro-5H-pyrrolo[3,4-c]pyridin-5-yl]methyl}-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid and N-methylhydroxylamine hydrochloride in a manner similar to step 2 of example 17. 1H NMR (MeOH-d4) δ ppm 8.80 (s, 1H), 8.28 (b, 1H), 7.72 (s, 1H), 7.32-7.31 (m, 1H), 7.05-7.02 (m, 1H), 7.00-6.93 (m, 1H), 5.59 (s, 2H), 3.88 (s, 2H), 3.42 (s, 3H), 3.28-3.26 (m, 2H), 2.98-2.96 (m, 1H), 2.83-2.80 (m, 1H), 2.58-2.56 (m, 1H), 2.48-2.44 (m, 2H), 2.27-2.25 (m, 1H), 1.85-1.82 (m, 1H), 1.63-1.59 (m, 1H). LCMS (APCI, M+H+): 470.15. HPLC: 96% purity.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.C(N(CC)CC)C.Cl[C:23]([O:25][C:26]1[CH:31]=[CH:30][C:29]([N+:32]([O-:34])=[O:33])=[CH:28][CH:27]=1)=[O:24]>C1COCC1>[N+:32]([C:29]1[CH:28]=[CH:27][C:26]([O:25][C:23]([N:12]2[CH2:11][CH2:10][N:9]([C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])[CH2:14][CH2:13]2)=[O:24])=[CH:31][CH:30]=1)([O-:34])=[O:33]
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Reactant: Fc1ccc(N2CCNCC2)c(F)c1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=C(Oc1ccc([N+](=O)[O-])cc1)N1CCN(c2ccc(F)cc2F)CC1
Temperature: 0 °C
Reaction time: 8 h
Yield: 62.6 %

Procedure:
1-(2,4-Difluoro-phenyl)-piperazine (3.70 g, 18.9 mmol) and triethylamine (2.8 mL, 19.8 mmol) were dissolved in anhydrous THF (30 mL) under nitrogen and the reaction mixture was cooled to 0° C. 4-Nitrophenyl chloroformate (3.8 g, 18.9 mmol), dissolved in anhydrous THF (25 mL), was added dropwise and the reaction mixture was stirred at room temperature overnight. The solvent was removed in vacuo and the residue triturated with water, and then filtered. The yellow solid was recrystallised from a mixture of hexane and toluene(3:7) using charcoal to give 4-(2,4-difluorophenyl)-piperazine-1-carboxylic acid 4-nitrophenyl ester (4.3 g, 63%) as a yellow crystalline solid.
Reaction SMILES: Cl[C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[C:9](=[NH:22])([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[C:9](=[N:22][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][N:3]=1)([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: N=C(c1ccccc1)c1ccccc1
Reactant: Fc1cccnc1Cl
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Product: Fc1cccnc1N=C(c1ccccc1)c1ccccc1
Temperature: 95 °C
Yield: 111.7 %

Procedure:
A mixture of 2-chloro-3-fluoropyridine (21.0 g, 0.16 mol), benzophenone imine (32.3 g, 0.18 mol), Cs2CO3 (73.0 g, 0.23 mol), BINAP (5.96 g, 9.6 mmol), palladium(II) acetate (1.45 g, 6.4 mmol) and toluene (370 ml) were heated to 95° C. for 42 h, then cooled, filtered and the residue extracted with further toluene (2×210 ml). The filtrate was washed with 0.5 N hydrochloric acid (200 ml) and saturated aqueous NaHCO3 (200 ml), dried over anhydrous MgSO4 and concentrated in vacuo, affording crude benzhydrylidene(3-fluoropyridin-2-yl)amine as a brown oil (49.4 g) which was used directly without further purification: m/z (ES+) 277 (100%, [MH]+)
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:11]([C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1)O.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1
Reactant: OC(c1cccnc1)c1c[nH]c2ccc(F)cc12
Agent: CC[SiH](CC)CC
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Fc1ccc2[nH]cc(Cc3cccnc3)c2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 68.2 %

Procedure:
A suspension of (5-fluoro-1H-indole-3-yl)-pyridin-3-yl-methanol (5.00 g, 21 mmol) in methylene chloride is treated with triethylsilane (3.70 ml, 23 mmol) and trifluoroacetic acid (TFA), stirred at room temperature overnight, and concentrated in vacuo. The resultant residue is basified with 2.5 N NaOH and saturated NaHCO3, and extracted with methylene chloride. The extracts are combined, dried over Na2SO4 and concentrated in vacuo. This residue is purified by column chromatography (50%EtOAc/CH2Cl2) to give the title compound as a pale orange solid 3.24 g (68%) mp 109-112° C., identified by NMR and mass spectral analyses.
Reaction SMILES: [Cl:1][C:2]1[C:7]([NH:8][CH2:9][C:10]2[CH:15]=[C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=3)[CH:13]=[CH:12][C:11]=2[F:23])=[C:6]([F:24])[CH:5]=[CH:4][C:3]=1[OH:25].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35].O>CC(C)=O>[Cl:1][C:2]1[C:7]([NH:8][CH2:9][C:10]2[CH:15]=[C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=3)[CH:13]=[CH:12][C:11]=2[F:23])=[C:6]([F:24])[CH:5]=[CH:4][C:3]=1[O:25][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35]
Reactant: Oc1ccc(F)c(NCc2cc(-c3cccc(F)c3)ccc2F)c1Cl
Reactant: CCOC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CC(C)=O
Product: CCOC(=O)COc1ccc(F)c(NCc2cc(-c3cccc(F)c3)ccc2F)c1Cl
Reaction time: 0.5 h
Yield: 86.1 %

Procedure:
To a solution of 2-chloro-4-fluoro-3-[[2-fluoro-5-(3-fluorophenyl)phenyl]methylamino]phenol (144 mg, 0.40 mmol, 1.0 eq) in acetone (3 mL) was added Cs2CO3 (193.5 mg, 0.59 mmol, 1.5 eq). The reaction mixture was stirred for 30 min, then ethyl 2-bromoacetate (79.3 mg, 0.48 mmol, 1.2 eq) was added. The reaction mixture was stirred at room temperature for 1 h and the resulting mixture poured into water and extracted with EtOAc. The organic extract was washed with water and brine, dried (Na2SO4), filtered, and evaporated in vacuo. The residue obtained was purified by column chromatography (EtOAc:petroleum ether, 1:20 to 1:10) to give the title compound as an oil (155 mg, 87%).
Reaction SMILES: [CH2:1]([C:3]1[N:8]=[C:7](S(C)(=O)=O)[N:6]=[C:5]([C:13]([OH:15])=[O:14])[CH:4]=1)[CH3:2].[CH2:16]([NH2:18])[CH3:17]>C1COCC1.O>[CH2:1]([C:3]1[N:8]=[C:7]([NH:18][CH2:16][CH3:17])[N:6]=[C:5]([C:13]([OH:15])=[O:14])[CH:4]=1)[CH3:2]
Reactant: CCN
Reactant: CCc1cc(C(=O)O)nc(S(C)(=O)=O)n1
Solvent: O
Solvent: C1CCOC1
Product: CCNc1nc(CC)cc(C(=O)O)n1
Temperature: 70 °C
Reaction time: 8 h

Procedure:
To a solution of 6-ethyl-2-methanesulfonyl-pyrimidine-4-carboxylic acid (325 mg, 1.41 mmol) in THF (5 mL) is added 70% ethylamine in water (2.0 mL). The mixture is stirred at 70° C. overnight. It is then evaporated to dryness and purified by prep. TLC (DCM/7N NH3 in MeOH 4/1) to give 6-ethyl-2-ethylamino-pyrimidine-4-carboxylic acid as a yellow oil (200 mg); LC-MS: tR=0.58 min, [M+H]+=194.07. 1H NMR (CDCl3): δ 1.34 (m, 6H), 2.84 (d, J=7.5 Hz, 2H), 3.64 (m, 2H), 7.26 (s, 1H), 11.0 (s br, 1H).
Reaction SMILES: [C:1]([O:4][CH2:5][C@H:6]1[C:14]2[C:9](=[CH:10][C:11]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[C:12]([NH:15][CH:16]([C:18]([O:20][CH3:21])=[O:19])[CH3:17])[CH:13]=2)[N:8]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:7]1)(=[O:3])[CH3:2].[N+](C1C=CC(C(O)=O)=CC=1)([O-])=O>CC(N(C)C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[O-2].[O-2].[Mn+4]>[C:1]([O:4][CH2:5][C@H:6]1[C:14]2=[C:13]3[C:12](=[C:11]([O:22][CH2:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH:10]=[C:9]2[N:8]([C:30]([O:32][C:33]([CH3:35])([CH3:34])[CH3:36])=[O:31])[CH2:7]1)[NH:15][C:16]([C:18]([O:20][CH3:21])=[O:19])=[CH:17]3)(=[O:3])[CH3:2]
Reactant: COC(=O)C(C)Nc1cc2c(cc1OCc1ccccc1)N(C(=O)OC(C)(C)C)C[C@H]2COC(C)=O
Agent: [Mn+4]
Agent: [Pd+2]
Agent: CC(=O)[O-]
Solvent: CC(=O)N(C)C
Product: COC(=O)c1cc2c3c(cc(OCc4ccccc4)c2[nH]1)N(C(=O)OC(C)(C)C)C[C@H]3COC(C)=O
Yield: 23.2 %

Procedure:
5.82 g (11.7 mmole) of (3S)-3-acetoxymethyl-5-[1-(methoxycarbonyl)ethyl]amino-6-benzyloxy-1-t-butoxycarbonylindoline, 5.24 g (23.4 mmole) of palladium acetate, 1.52 g (17.5 mmole) of manganese dioxide, and 1.95 g (11.7 mmole) of 4-nitrobenzoic acid were heated in 500 ml of dimethylacetamide at 90° C. for 18 hours. The reaction mixture was concentrated, ethyl acetate was added to the obtained residue, insoluble matter was removed by filtration, and the obtained filtrate was concentrated to give a residue. The residue was then purified by silica gel column chromatography with changing an eluate from benzene:ethyl acetate (5:1) to benzene:ethyl acetate (10:1) to give 1.34 g of methyl (1S)-1-acetoxymethyl-5-benzyloxy-3-t-butoxycarbonyl-1,2,3,6-tetrahydropyrrolo[3,2-e]indole-7-carboxylate. Yield, 23%. Mp. 128.5-129.5° C. (isopropyl ether). Elemental analysis: Calculated as C27H30N2O7 : C,65.57; H,6.11; N,5.66 Found: C,65.40; H,6.05; N,5.64 NMR (CDCl3) δ: 1.58 (9H, s), 2.10 (3H, s), 3.80-3.92 (2H, m), 3.92 (3H, s), 4.06 (1H, t, J=10.3 Hz), 4.15 (1H, dd, J=9.3, 11.2 Hz), 4.48 (1H, dd, J=5.4, 10.8 Hz), 5.22 (2H, s), 7.13 (1H, d, J=2.4 Hz), 7.39-7.48 (5H, m), 7.82 (1H, brs), 9.00 (1H, s). [α]D25 =-11.1° (c 0.21, methanol).
Reaction SMILES: [CH3:1][S:2][CH:3]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12](=[O:19])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:7]=1)[C:4]#[N:5].[CH3:20][O-].[Na+].CI.[Cl-].[NH4+]>CO>[CH3:1][S:2][C:3]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12](=[O:19])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:7]=1)([CH3:20])[C:4]#[N:5]
Reactant: CSC(C#N)c1cccc(C(=O)c2ccccc2)c1
Reactant: C[O-]
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CI
Solvent: CO
Product: CSC(C)(C#N)c1cccc(C(=O)c2ccccc2)c1
Yield: 73 %

Procedure:
433 mg of alpha-(methylthio)(m-benzoylphenyl)-acetonitrile was dissolved in 2 ml of anhydrous methanol. The solution was stirred in an atmosphere of argon under ice cooling. Then, 0.65 ml of a 2.5 M methanol solution of sodium methoxide was added, and then 0.15 ml of methyl iodide was added dropwise. Under ice cooling, the mixture was stirred for 1 hour, and an aqueous solution of ammonium chloride (0.5 g/30 ml) was added. The mixture was extracted with 20 ml of methylene chloride three times. The extract was washed with 10 ml of water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel; methylene chloride) to afford 334 mg (yield 73%) of alpha-(methylthio)-alpha-(m-benzoylphenyl)-propionitrile as a pale yellow oil.
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][CH2:10][C:11]([OH:13])=O.[NH:16]1[CH2:21][CH2:20][C:19]2([C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[NH:23][C:22]2=[O:30])[CH2:18][CH2:17]1>>[F:14][C:2]([F:1])([F:15])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][CH2:10][C:11]([N:16]1[CH2:21][CH2:20][C:19]2([C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[NH:23][C:22]2=[O:30])[CH2:18][CH2:17]1)=[O:13]
Reactant: O=C1Nc2ccccc2C12CCNCC2
Reactant: O=C(O)CCc1ccccc1C(F)(F)F
Product: O=C(CCc1ccccc1C(F)(F)F)N1CCC2(CC1)C(=O)Nc1ccccc12

Procedure:
The title compound was prepared following a procedure analogous to that described in Example 31 using 3-(2-(trifluoromethyl)phenyl)propanoic acid and spiro[indoline-3,4′-piperidin]-2-one. LC-MS Method 3 tR=1.157, min, m/z=403; 1H NMR (CDCl3) 1.39 (m, 2H), 1.47 (m, 2H), 1.65 (m, 2H), 1.78 (m, 3H), 2.62 (m, 2H), 3.15 (m, 2H), 3.61 (m, 2H), 3.83 (m, 2H), 4.17 (m, 1H), 6.83 (d, 1H), 6.97 (m, 1H), 7.15 (m, 2H), 7.26 (m, 1H), 7.38 (m, 1H), 7.43 (m, 1H), 7.58 (d, 1H), 7.84 (s, 1H).
Reaction SMILES: [F:1]C(F)(F)C(C(F)(F)F)=C(C(F)(F)C(F)(F)F)C(F)(C(F)(F)F)C(F)(F)F.FC([Si](C)(C)C)(F)F.[F-].[K+].FC(F)(F)F.[F:43][C:44]([F:75])([F:74])[C:45](C(F)(F)F)=[C:46]([C:60]([F:69])([C:65]([F:68])([F:67])[F:66])[C:61]([F:64])([F:63])[F:62])[C:47]([C:56]([F:59])([F:58])[F:57])([C:52]([F:55])([F:54])[F:53])[C:48]([F:51])([F:50])[F:49]>CN(C)C=O>[F:75][C:44]([F:43])([F:74])[C:45]([F:1])=[C:46]([C:60]([F:69])([C:61]([F:64])([F:62])[F:63])[C:65]([F:67])([F:68])[F:66])[C:47]([C:56]([F:59])([F:57])[F:58])([C:48]([F:51])([F:49])[F:50])[C:52]([F:53])([F:55])[F:54]
Reactant: FC(F)(F)C(=C(C(F)(F)C(F)(F)F)C(F)(C(F)(F)F)C(F)(F)F)C(F)(F)F
Reactant: FC(F)(F)C(=C(C(F)(C(F)(F)F)C(F)(F)F)C(C(F)(F)F)(C(F)(F)F)C(F)(F)F)C(F)(F)F
Agent: C[Si](C)(C)C(F)(F)F
Agent: FC(F)(F)F
Agent: [F-]
Solvent: CN(C)C=O
Product: FC(=C(C(F)(C(F)(F)F)C(F)(F)F)C(C(F)(F)F)(C(F)(F)F)C(F)(F)F)C(F)(F)F
Temperature: 25 °C
Reaction time: 1 h

Procedure:
1 mmol (450 mg) of perfluoro(3-ethyl-2,4-dimethyl-2-pentene) and 4.0 mmol (568.8 mg) of trifluoromethyltrimethylsilane were weighed into a 10-ml fluororesin-made reaction container, then 1 ml of dimethyl formamide and 0.1 mmol of acidic potassium fluoride (KHF2, 7.8 mg) were added therein. A fluororesin-made magnetic stirrer was placed and the mixture was stirred vigorously for 1 hour at room temperature, and then 1.0 mmol of trifluoromethyltrimethylsilane (142.2 mg) and 0.1 mmol of acidic potassium fluoride (KHF2, 7.8 mg) were added and the mixture was further stirred vigorously for 1 hour at room temperature. After completion of the reaction, the transparent lower perfluorocarbon layer was analyzed by gas chromatography using a capillary column (NB-1, 0.25 μm, 1.5 mm ID×60 m). The yield of the main product perfluoro(2,4,4-trimethyl-3-isopropyl-2-pentene) was 74.5% by weight. As the by-product, perfluoro 4,4-dimethyl-3-isopropyl-2-pentene was obtained at the yield of 25.5% by weight. The starting material perfluoro(3-ethyl-2,4-dimethyl-2-pentene) was consumed completely by the reaction.
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[C:7]2[C:9]([C:13]3[N:23]([S:24]([C:27]4[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=4)(=[O:26])=[O:25])[C:16]4=[N:17][CH:18]=[CH:19][C:20]([CH2:21]O)=[C:15]4[CH:14]=3)=[CH:10][N:11]([CH3:12])[C:6]2=[CH:5][C:4]=1[O:34][CH3:35].S(Cl)([Cl:38])=O.CN(C=O)C.C(=O)([O-])O.[Na+]>ClCCl>[Cl:38][CH2:21][C:20]1[CH:19]=[CH:18][N:17]=[C:16]2[N:23]([S:24]([C:27]3[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=3)(=[O:26])=[O:25])[C:13]([C:9]3[C:7]4=[N:8][C:3]([O:2][CH3:1])=[C:4]([O:34][CH3:35])[CH:5]=[C:6]4[N:11]([CH3:12])[CH:10]=3)=[CH:14][C:15]=12
Reactant: O=S(Cl)Cl
Reactant: COc1cc2c(nc1OC)c(-c1cc3c(CO)ccnc3n1S(=O)(=O)c1ccc(C)cc1)cn2C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: COc1cc2c(nc1OC)c(-c1cc3c(CCl)ccnc3n1S(=O)(=O)c1ccc(C)cc1)cn2C
Reaction time: 2 h

Procedure:
To a solution of 4.2 g of [2-(5,6-dimethoxy-1-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]methanol in 50 cm3 of dichloromethane, at a temperature in the region of 20° C., are added 0.747 cm3 of thionyl chloride and 0.3 cm3 of DMF. The reaction medium is stirred at this same temperature for 2 hours. Ice is added and the reaction medium is then neutralized with saturated sodium hydrogencarbonate solution. After separation of the phases by settling, the organic phase is dried over magnesium sulfate, filtered and then concentrated under reduced pressure. After purification by flash-pack chromatography (SiO2, dichloromethane/ethyl acetate 95/05 by volume as eluents), 2.64 g of 3-[4-chloromethyl-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-5,6-dimethoxy-1-methyl-1H-pyrrolo[3,2-b]pyridine are obtained with the following characteristics:
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH:11]=O)=[CH:8][CH:7]=[CH:6][CH:5]=2.CCCCCC.[NH2:19]C1C=CC=CC=1>C1(C)C=CC=CC=1>[CH3:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH:11]=[NH:19])=[CH:8][CH:7]=[CH:6][CH:5]=2
Reactant: Cc1[nH]c2ccccc2c1C=O
Reactant: Nc1ccccc1
Solvent: CCCCCC
Solvent: Cc1ccccc1
Product: Cc1[nH]c2ccccc2c1C=N
Temperature: 70 °C
Reaction time: 3.5 h
Yield: 110.6 %

Procedure:
2-methylindole-3-carboxaldehyde (10 g, 0.06 mol) was mixed with hexane (40 ml), to which aniline (9.6 ml, 0.11 mol) was added and stirred at 70° C. for 3.5 hours under reflux. Then, toluene (20 ml) was added and dissolved. The mixture was then submitted to silica gel column chromatography. The column was eluted by a developing solvent of hexane/ethyl acetate=3/1 and a fraction containing the desired product was concentrated by distilling off the solvent, to obtain 10.5 g (yield: 75%) of 2-methylindole-3-carboxaldehyde imine. 1H-NMR spectra (chemical shift, ppm: in CDCl3): 2.63 (3H, s), 7.15-7.42 (8H, m), 8.19 (1H, s), 8.45-8.48 (1H, m), 8.69 (1H, s).