Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.CN(C)CCCN=C=NCC.[CH:13]1[C:22]2[C:17](=[CH:18][C:19]([C:23]([OH:25])=O)=[CH:20][CH:21]=2)[CH:16]=[CH:15][C:14]=1[C:26]([OH:28])=[O:27].OC1C2N=NNC=2C=CC=1.[CH2:39]([NH:41][CH2:42][CH3:43])[CH3:40]>CN(C)C=O>[CH2:39]([N:41]([CH2:42][CH3:43])[C:23]([C:19]1[CH:18]=[C:17]2[C:22](=[CH:21][CH:20]=1)[CH:13]=[C:14]([C:26]([OH:28])=[O:27])[CH:15]=[CH:16]2)=[O:25])[CH3:40]
Reactant: O=C(O)c1ccc2cc(C(=O)O)ccc2c1
Reactant: CCNCC
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: Oc1cccc2[nH]nnc12
Solvent: CN(C)C=O
Product: CCN(CC)C(=O)c1ccc2cc(C(=O)O)ccc2c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 59.3 %

Procedure:
1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (22.2 g, 115 mmol) was added to a solution of 2,6-naphthalenedicarboxylic acid (25 g, 115 mmol) and hydroxybenzotriazole (15.6 g, 115 mmol) in dimethylformamide (1800 ml) and the mixture was stirred at room temperature for 2 hours. Diethyl amine (34.3 ml, 345 mmol) was added and the solution was stirred overnight at room temperature. The solvent was then evaporated under reduced pressure and the crude was treated with 1N HCl (500 ml) and ethyl acetate (500 ml), insoluble compounds were filtered off and the phases were separated. The organic phase was extracted with 5% sodium carbonate (3×200 ml) and the combined aqueous solutions were acidified with concentrated HCl and extracted with ethyl acetate (3×200 ml). The organic solution was then washed with 1N HCl (6×100 ml), dried over anhydrous sodium sulphate and the solvent was removed under reduced pressure yielding 18.5 g (Yield 60%) of pure 6-(diethylaminocarbonyl)-2-naphthalenecarboxylic acid; m.p.=122-124° C.
Reaction SMILES: [CH:1]1([N:6]2[CH2:11][CH2:10][N:9]([C:12]([C:14]3[CH:15]=[C:16]4[C:20](=[CH:21][CH:22]=3)[NH:19][C:18]([C:23]([N:25]3[CH2:30][CH2:29][S:28](=[O:32])(=[O:31])[CH2:27][CH2:26]3)=[O:24])=[CH:17]4)=[O:13])[CH2:8][CH2:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[F:33][C:34]([F:45])([F:44])[C:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=1.N1C=CC=CC=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH:1]1([N:6]2[CH2:7][CH2:8][N:9]([C:12]([C:14]3[CH:15]=[C:16]4[C:20](=[CH:21][CH:22]=3)[N:19]([C:38]3[CH:39]=[CH:40][C:35]([C:34]([F:45])([F:44])[F:33])=[CH:36][CH:37]=3)[C:18]([C:23]([N:25]3[CH2:30][CH2:29][S:28](=[O:31])(=[O:32])[CH2:27][CH2:26]3)=[O:24])=[CH:17]4)=[O:13])[CH2:10][CH2:11]2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: O=C(c1ccc2[nH]c(C(=O)N3CCS(=O)(=O)CC3)cc2c1)N1CCN(C2CCCC2)CC1
Reactant: OB(O)c1ccc(C(F)(F)F)cc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=C(c1ccc2c(c1)cc(C(=O)N1CCS(=O)(=O)CC1)n2-c1ccc(C(F)(F)F)cc1)N1CCN(C2CCCC2)CC1
Yield: 15 %

Procedure:
The title compound was synthesized in analogy to example 66, from [5-(4-cyclopentyl-piperazine-1-carbonyl)-1H-indol-2-yl]-(1,1-dioxo-thiomorpholin-4-yl)-methanone (example 34), 4-(trifluoromethyl)phenylboronic acid, copper(II) acetate and pyridine in dichloromethane, to give the desired product as a light yellow solid (15%).
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:10]=[C:11]3[C:16](=[C:17]4[N:22]([CH3:23])[CH2:21][CH:20]=[CH:19][C:18]=24)[N:15]=[CH:14][N:13]([C@H:24]2[CH2:29][CH2:28][CH2:27][CH2:26][C@@H:25]2[OH:30])[C:12]3=[O:31])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:38][N:39]1[CH:43]=[C:42](B2OC(C)(C)C(C)(C)O2)[CH:41]=[N:40]1>C1COCC1.C(OCC)(=O)C.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[OH:30][C@H:25]1[CH2:26][CH2:27][CH2:28][CH2:29][C@@H:24]1[N:13]1[C:12](=[O:31])[C:11]2[C:16](=[C:17]3[N:22]([CH3:23])[CH2:21][CH:20]=[CH:19][C:18]3=[C:9]([CH2:8][C:5]3[CH:6]=[N:7][C:2]([C:42]4[CH:41]=[N:40][N:39]([CH3:38])[CH:43]=4)=[CH:3][CH:4]=3)[CH:10]=2)[N:15]=[CH:14]1
Reactant: CN1CC=Cc2c(Cc3ccc(Cl)nc3)cc3c(=O)n([C@H]4CCCC[C@@H]4O)cnc3c21
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Agent: CC(C)(C)[P]([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C(C)(C)C)C(C)(C)C
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CN1CC=Cc2c(Cc3ccc(-c4cnn(C)c4)nc3)cc3c(=O)n([C@H]4CCCC[C@@H]4O)cnc3c21
Temperature: 100 °C

Procedure:
To a solution of 6-[(6-chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclohexyl]-10-methyl-9,10-dihydropyrido[3,2-h]quinazolin-4(3H)-one (Example 1, 0.040 g, 0.092 mmol) in 2 mL of THF under an atmosphere of nitrogen was added aqueous cesium carbonate (1 M, 0.18 mL, 0.18 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.057 g, 0.28 mmol), and bis(tri-tert-butylphosphine)palladium(0) (4.0 mg, 0.0078 mmol). The reaction was heated at 100° C. for 16 h, cooled to rt, diluted with ethyl acetate, and washed with saturated aqueous sodium bicarbonate and brine. The solution was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-5% methanol in dichloromethane, to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 483.1 for [M+H]+: 1H NMR (400 MHz, CD3OD) δ 8.92 (s, 1H), 8.52 (d, J=8.6 Hz, 1H), 8.40 (s, 1H), 8.08 (s, 1H), 7.95 (br s, 2H), 7.61-7.39 (m, 3H), 4.78 (s, 2H), 4.49 (s, 2H), 4.23 (br s, 1H), 3.92 (s, 3H), 3.74 (br s, 1H), 3.20 (s, 3H), 2.11 (br s, 1H), 1.83-1.63 (m, 5H), 1.29-1.23 (m, 2H).
Reaction SMILES: [CH3:1][C@@:2]12[CH2:9][CH2:8][CH2:7][N:6]1[C@@H:5]([C:10]([Cl:13])([Cl:12])[Cl:11])[O:4][C:3]2=[O:14].[CH:15](NC(C)C)(C)[CH3:16].ClC(Cl)(Cl)[C@H]1OC(=O)[C@H]2N1CCC2.C(Br)C=C>>[CH2:1]([C@@:2]12[CH2:9][CH2:8][CH2:7][N:6]1[C@@H:5]([C:10]([Cl:13])([Cl:12])[Cl:11])[O:4][C:3]2=[O:14])[CH:15]=[CH2:16]
Reactant: CC(C)NC(C)C
Reactant: C[C@@]12CCCN1[C@@H](C(Cl)(Cl)Cl)OC2=O
Agent: O=C1O[C@H](C(Cl)(Cl)Cl)N2CCC[C@@H]12
Solvent: C=CCBr
Product: C=CC[C@@]12CCCN1[C@@H](C(Cl)(Cl)Cl)OC2=O
Yield: 40 %

Procedure:
(Wang et al. Synlett 1999, 1, 33) The reaction was carried out following a similar procedure to that described for the preparation of oxazolidinone 8 using n-butyllithium (1.31 M, 9.93 cm3, 13.0 mmol), diisopropylamine (1.82 cm3, 13.0 mmol), oxazolidinone 7 (2.10 g, 8.7 mmol) and allyl bromide (2.25 cm3, 26.0 mmol) to afford oxazolidinone 10 (1.48 g, 60%) as a light orange oil for which the NMR data were in agreement with the literature.
Reaction SMILES: [CH3:1][C:2]([CH3:31])([CH3:30])[CH2:3][C:4]([NH:6][C:7]1[C:8]([CH3:29])=[C:9](B(O)O)[C:10]2[O:14][CH2:13][CH:12]([C:15]3[CH:20]=[CH:19][C:18]([CH:21]([CH3:23])[CH3:22])=[CH:17][CH:16]=3)[C:11]=2[C:24]=1[CH3:25])=[O:5].[C:32]([C:35]1[S:36][C:37](Br)=[CH:38][CH:39]=1)(=[O:34])[CH3:33]>CCCCCC.C(OCC)(=O)C>[C:32]([C:35]1[S:36][C:37]([C:9]2[C:10]3[O:14][CH2:13][CH:12]([C:15]4[CH:20]=[CH:19][C:18]([CH:21]([CH3:22])[CH3:23])=[CH:17][CH:16]=4)[C:11]=3[C:24]([CH3:25])=[C:7]([NH:6][C:4](=[O:5])[CH2:3][C:2]([CH3:1])([CH3:30])[CH3:31])[C:8]=2[CH3:29])=[CH:38][CH:39]=1)(=[O:34])[CH3:33]
Reactant: Cc1c(NC(=O)CC(C)(C)C)c(C)c2c(c1B(O)O)OCC2c1ccc(C(C)C)cc1
Reactant: CC(=O)c1ccc(Br)s1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CC(=O)c1ccc(-c2c(C)c(NC(=O)CC(C)(C)C)c(C)c3c2OCC3c2ccc(C(C)C)cc2)s1
Yield: 65 %

Procedure:
Using (5-((3,3-dimethylbutanoyl)amino)-3-(4-isopropylphenyl)-4,6-dimethyl-2,3-dihydro-1-benzofuran-7-yl)boronic acid obtained in Example 116 and 2-acetyl-5-bromothiophene, the title compound was synthesized in the same manner as in Example 107. Yield: 65%. Melting point: 157-158° C. (hexane-ethyl acetate).
Reaction SMILES: [CH:1]12[O:7][CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6]2.[CH3:8][NH:9][CH3:10]>>[CH3:8][N:9]([CH3:10])[CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[OH:7]
Reactant: C1CCC2OC2C1
Reactant: CNC
Product: CN(C)C1CCCCC1O
Reaction time: 8 h

Procedure:
A mixture of 50.0 g of cyclohexene oxide and 100 ml of 25 percent aqueous dimethylamine was heated with stirring at 145° in a small autoclave for 8 hours. While the mixture was being concentrated to dryness at 50° on a film evaporator, absolute ethanol was added periodically to aid in removal of water. The residue was distilled through a Nester-Faust spinning band column to give 53.0 g of 2-dimethylamino-1-cyclohexanol, b.p. 64.1 - 64.2/2.4 mm. The ir curve was consistent with the assigned structure.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][C:9]([NH:12][S:13]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][C:17]=2[N+:26]([O-])=O)(=[O:15])=[O:14])=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.O.NN>[Ni].CO>[NH2:26][C:17]1[CH:18]=[C:19]([C:22]([F:24])([F:23])[F:25])[CH:20]=[CH:21][C:16]=1[S:13]([NH:12][C:9]1[CH:10]=[CH:11][C:2]([Cl:1])=[C:3]2[C:8]=1[N:7]=[CH:6][CH:5]=[CH:4]2)(=[O:14])=[O:15]
Reactant: O=[N+]([O-])c1cc(C(F)(F)F)ccc1S(=O)(=O)Nc1ccc(Cl)c2cccnc12
Agent: [Ni]
Agent: NN
Solvent: O
Solvent: CO
Product: Nc1cc(C(F)(F)F)ccc1S(=O)(=O)Nc1ccc(Cl)c2cccnc12
Yield: 26.7 %

Procedure:
In the similar fashion using route 6 general procedure 14, N-(5-chloroquinolin-8-yl)-2-nitro-4-trifluoromethylbenzenesulfonamide (Intermediate 156) (120 mg, 0.28 mmol), Raney nickel (24 mg, 20% wt), hydrazine hydrate (40 μl, 0.84 mmol), MeOH (3 ml) gave the title compound (30 mg, 27%) after purification by column chromatography with DCM/MeOH (199:1) as the eluent.
Reaction SMILES: [C:1]1([CH:7]2[NH:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[NH:9][C:8]2=[O:17])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:18]([O-])=[O:19].[Na+]>Cl.O>[N:18]([N:16]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[NH:9][C:8](=[O:17])[CH:7]1[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)=[O:19]
Reactant: O=C1Nc2ccccc2NC1c1ccccc1
Reactant: O=N[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Product: O=NN1c2ccccc2NC(=O)C1c1ccccc1
Temperature: 5 °C
Reaction time: 1 h
Yield: 98.7 %

Procedure:
A suspension of 3,4-dihydro-3-phenylquinoxalin-2(1H)-one (430 mg, 1.9 mmol) in 3N HCl (30 mL) was stirred at 5° C. Sodium nitrite (150 mg, 2.17 mmol) in water (1 mL) was added dropwise and stirring was continued for 1 h. The reaction mixture was extracted with DCM. The organic layer was dried over sodium sulfate and concentrated under vacuum to obtain 475 mg of 3,4-dihydro-4-nitroso-3-phenylquinoxalin-2(1H)-one.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:4]=1[CH2:12][C:13]([OH:15])=O.C(Cl)CCl.C[CH2:21][N:22](CC)[CH2:23]C.Cl.CNC>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:4]=1[CH2:12][C:13]([N:22]([CH3:23])[CH3:21])=[O:15]
Reactant: COc1ccc([N+](=O)[O-])cc1CC(=O)O
Reactant: CCN(CC)CC
Agent: CNC
Agent: Cl
Solvent: ClCCl
Solvent: ClCCCl
Product: COc1ccc([N+](=O)[O-])cc1CC(=O)N(C)C

Procedure:
2-(2-Methoxy-5-nitrophenyl)acetic acid (17.1 g, 1 eq, Step B), EDC (18.6 g, 1.2 eq.), Et3N (9.8 g, 13.6 mL, 1.2 eq) and dimethylamine hydrochloride (7.9 g, 1.2 eq.) in 150 mL of CH2Cl2 were stirred together with exclusion of air overnight. CH2Cl2 (150 mL) was added and the mixture was washed twice with 1M HCl, twice with 1M NaOH, water and brine. Removal of the solvent under reduced pressure followed by silica gel chromatography (90:10 CH2Cl2:EtOAc) afforded pure 2-(2-methoxy-5-nitrophenyl)-N,N-dimethyl-acetamide as a white solid.
Reaction SMILES: ClC(C1C(CC2CC2)=C(C(OC)=O)C(C(F)F)=NC=1C(F)(F)F)=O.[CH:25]1([CH2:28][C:29]2[C:34]([C:35]#[N:36])=[C:33]([C:37]([F:40])([F:39])[F:38])[N:32]=[C:31]([CH:41]([F:43])[F:42])[C:30]=2[C:44]([O:46][CH3:47])=[O:45])[CH2:27][CH2:26]1.C(NCC)C.[SH2:53]>CN(C=O)C>[NH2:36][C:35](=[S:53])[C:34]1[C:29]([CH2:28][CH:25]2[CH2:27][CH2:26]2)=[C:30]([C:44]([O:46][CH3:47])=[O:45])[C:31]([CH:41]([F:43])[F:42])=[N:32][C:33]=1[C:37]([F:40])([F:38])[F:39]
Reactant: S
Reactant: COC(=O)c1c(C(F)F)nc(C(F)(F)F)c(C#N)c1CC1CC1
Agent: COC(=O)c1c(C(F)F)nc(C(F)(F)F)c(C(=O)Cl)c1CC1CC1
Solvent: CN(C)C=O
Solvent: CCNCC
Product: COC(=O)c1c(C(F)F)nc(C(F)(F)F)c(C(N)=S)c1CC1CC1
Temperature: 50 °C
Reaction time: 1 h
Yield: 80 %

Procedure:
Methyl 5-chlorocarbonyl-4-(cyclopropylmethyl)-2-(difluoromethyl)-6-(trifluoromethyl)-3-pyridinecarboxylate (example B3 of U.S. Pat. No. 5,156,670) was converted to methyl 4-(cyclopropylmethyl)-5-cyano-2-(difluoromethyl)-6-(trifluoromethyl)-3-pyridinecarboxylate by the procedure similar to example 88 and 92 of U.S. Pat. No. 4,692,184. A solution of 20 g (60 mmol) of this cyano compound and 0.62 g (6 mmol) of diethylamine in 60 ml of DMF was heated to 50° C. Hydrogen sulfide gas was introduced into this solution. When absorption of hydrogen sulfide was complete the reaction mixture was stirred at 50° C. for 1 h and poured into water and extracted with ether. The ether extract was washed with brine, dried (MgSO4), and concentrated in vacuo. The residue was kugelrohr distilled to give 17.7 g (80% yield) of yellow oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:9]=[C:8]([O:10]C)[CH:7]=[CH:6][C:4]=1[NH2:5].C[O:13][C:14]1[C:22]([O:23]C)=[CH:21][CH:20]=[CH:19][C:15]=1C(O)=O>>[OH:10][C:8]1[CH:7]=[CH:6][C:4]2[N:5]=[C:1]([C:21]3[CH:20]=[CH:19][CH:15]=[C:14]([OH:13])[C:22]=3[OH:23])[O:2][C:3]=2[CH:9]=1
Reactant: COc1cccc(C(=O)O)c1OC
Reactant: COc1ccc(N)c(OC)c1
Product: Oc1ccc2nc(-c3cccc(O)c3O)oc2c1

Procedure:
The title compound was prepared in substantially the same manner as described in Example 1, from 2,4-dimethoxyaniline, and 2,3-dimethoxybenzoic acid and was obtained as a tan solid, m.p. 256–258° C.; MS m/e 244 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH2:7][CH:8]([CH:13]([C:15](=O)[CH3:16])[CH3:14])[C:9]2=O)=[CH:5][CH:4]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.O.[NH2:30][CH2:31][C@H:32]([OH:34])[CH3:33]>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH2:7][C:8]3[C:13]([CH3:14])=[C:15]([CH3:16])[N:30]([CH2:31][C@H:32]([OH:34])[CH3:33])[C:9]=32)=[CH:5][CH:4]=1
Reactant: C[C@@H](O)CN
Reactant: COc1ccc2c(c1)C(=O)C(C(C)C(C)=O)C2
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: COc1ccc2c(c1)-c1c(c(C)c(C)n1C[C@@H](C)O)C2
Reaction time: 1.42 h
Yield: 70.2 %

Procedure:
A solution of 1.5 g of rac-6-methoxy-2-(3-oxo-2-butyl)-1-indanone and 80 mg of p-toluenesulfonic acid in 70 ml of anhydrous toluene was heated on a water separator. A solution of 1.94 g of (R)-1-amino-2-propanol in 20 ml of anhydrous toluene was added dropwise to the boiling solution over a period of 5 minutes. Subsequently, the mixture was boiled for an additional 85 minutes, during which the solvent was reduced to a volume of 20 ml. The cooled reaction mixture was purified by column chromatography on silica gel (ethyl acetate/toluene 2:3). 1.23 g (70%) of (R)-1-(7-methoxy-2,3-dimethyl-1,4-dihydro-indeno[1,2-b]pyrrol-1-yl)-propan-2-ol were obtained as a yellow oil.
Reaction SMILES: [CH3:1][S:2][CH2:3][C:4](OCC)=[O:5].S(Cl)(Cl)(=O)=O.[NH2:14][C:15]1[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][CH:16]=1.CN(C1C2C(N(C)C)=CC=CC=2C=CC=1)C>ClCCl>[CH3:22][O:21][C:19]([C:18]1[CH:23]=[C:24]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:4](=[O:5])[CH:3]2[S:2][CH3:1])=[O:20]
Reactant: COC(=O)c1ccc(N)cc1
Reactant: CCOC(=O)CSC
Agent: CN(C)c1cccc2cccc(N(C)C)c12
Solvent: ClCCl
Solvent: O=S(=O)(Cl)Cl
Product: COC(=O)c1ccc2c(c1)C(SC)C(=O)N2
Temperature: -70 °C
Yield: 42.1 %

Procedure:
A solution of 2.66 g (20.0 mmol) of ethyl (methylthio)acetate dissolved in 200 mL of dichioromethane was cooled with stirring to −70° C. and 2.7 g (20.0 mmol) of sulfuryl chloride was added. The reaction was stirred for 30 min. at −70° C., and a solution of 3.0 g (20 mol) of methyl 4-aminobenzoate and 4.3 g (20 mmol) of Proton Sponge® in 250 mL of dichloromethane was added dropwise over 1 h. The resulting pink slurry was treated with 2.3 9 (23 mmol) of TEA in one portion, and the solution was allowed to warm to rt. The solution was washed with three 250-mL portions of water, dried over MgSO4, and concentrated to give an oil. This was chromatographed on silica gel eluting with hexane:EtOAc (1:1) to yield 2.0 g (42% yield) of 3-methylthio-2-oxo-2,3-dihydro-1H-indole-5-carboxylic acid methyl ester: 1H NMR (DMSO-d6): δ 1.97 (s, 3H), 3.35 (s, 3H), 4.67 (s, 1H), 6.97 (d, J=8.2 Hz, 1H), 7.84 (s, 1H), 7.91 (d, J=8.2 Hz, 1H), 10.97 (s, 1H), solution of 2.0 g (8.4 mmol) of 3-methylthio-2-oxo-2,3-dihydro-1H-indole-5-carboxylic acid methyl ester in 20 mL of acetic acid was treated with 10 g of zinc powder. The reaction mixture was stirred for 2 h at rt, filtered through celite and concentrated to dryness. The residue was chromatographed on silica gel eluting with hexane:EtOAc (1:1) to yield 1.6 g (99% yield) of 2-oxo-2,3-dihydro-1H-indole-5-carboxylic acid methyl ester as a pink solid: 1H NMR (DMSO-d6): δ 3.52 (s, 2H), 3.77 (s, 3H), 6.87 (d, J=8.2 Hz, 1H), 7.74 (s, J=1H), 7.80 (d, J=8.2 Hz, 1H), 10.72 (br s, 1H). Conversion to the 3-dimethylaminomethylene-2-oxo-2,3-dihydro-1H-indole-5-carboxylic acid methyl ester (mixture of E and Z isomers) was carried out via Procedure G in 49% yield: 1H NMR (DMSO-d6): δ 3.29 Z (s, 6H), 3.31 E (s, 6H), 3.76 Z (s, 3H), 3.76 E (s, 3H), 6.74 Z (d, J=8.1 Hz, 1H), 6.81 E (d, J=8.2 Hz, 1H), 7.47-7.50 Z (m, 1H), 7.50-7.52 E (m, 1H), 7.57 E (dd, J=1.3, 8.2 Hz, 1H), 7.74 Z (s, 1H), 7.89 Z (s, 1H), 7.94 E (s, 1H), 10.33 Z (bs, 1H), 10.43 E (bs, 1H). The title compound was prepared in 41% yield from 3-[(dimethylamino)methylene]oxindole-5-carboxylic acid methyl ester and 4-aminobenzenesulfonamide according to Procedure J: 1H NMR (DMSO-d6): δ 3.81 (s, 3H), 6.92 (d, J=8.2 Hz, 1H), 7.26 (s, 2H), 7.60 (d, J=8.4 Hz, 2H), 7.69 (d, J=8.2 Hz, 1H), 7.75 (d, J=8.4 Hz, 2H), 8.29 (s, 1H), 8.86 (d, J=12.4 Hz, 1H), 10.80 (d, J=12.4 Hz, 1H), 10.94 (s, 1H); APCI−MS m/z 372 (M−1)−. Anal. Calcd for C17H15N3O5S: C, 54.68, H, 4.05; N, 11.25; S, 8.59. Found C, 54.65, H, 4.12; N, 11.17; S. 8.49.
Reaction SMILES: [CH2:1]([C:5]1[NH:9][C:8]2[CH:10]=[C:11]3[C:16](=[CH:17][C:7]=2[N:6]=1)[CH:15]=[CH:14][CH:13]=[CH:12]3)[CH2:2][CH2:3][CH3:4].Br[CH2:19][C:20]1[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=1>>[CH2:1]([C:5]1[N:6]([CH2:19][C:20]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=2)[C:7]2[CH:17]=[C:16]3[C:11](=[CH:10][C:8]=2[N:9]=1)[CH:12]=[CH:13][CH:14]=[CH:15]3)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc2cc3ccccc3cc2[nH]1
Reactant: N#Cc1ccc(CBr)cc1
Product: CCCCc1nc2cc3ccccc3cc2n1Cc1ccc(C#N)cc1
Yield: 67.8 %

Procedure:
Using the procedure of Step B of Example 1, 449 mg of the product of Step A and 392 mg of 4-bromomethyl benzonitrile were reacted to obtain 460 mg of the desired product melting at 138° C. after crystallization from ethyl ether.
Reaction SMILES: [CH2:1]([C:4]1[CH:13]=[CH:12][C:11]2[N:10]=[CH:9][CH:8]=[CH:7][C:6]=2[C:5]=1[OH:14])[CH:2]=[CH2:3]>ClCCl.CC#N.CC#N.Cl[Pd]Cl>[CH:1](/[C:4]1[CH:13]=[CH:12][C:11]2[N:10]=[CH:9][CH:8]=[CH:7][C:6]=2[C:5]=1[OH:14])=[CH:2]\[CH3:3]
Reactant: C=CCc1ccc2ncccc2c1O
Agent: Cl[Pd]Cl
Solvent: ClCCl
Solvent: CC#N
Product: C/C=C/c1ccc2ncccc2c1O

Procedure:
Treatment of 6-allylquinolin-5-ol in dichloromethane with bis(acetonitrile)dichloropalladium (II) following the procedure described for Example 3c affords 6-[(1E)-prop-1-enyl]quinolin-5-ol.
Reaction SMILES: Br[C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[S:4][C:3]=1[CH3:11].CCCCCC.C([Li])CCC.[CH:23]1([CH:29]=[O:30])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1.[Cl-].[NH4+]>O1CCCC1>[CH:23]1([CH:29]([C:2]2[C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=3[S:4][C:3]=2[CH3:11])[OH:30])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1
Reactant: O=CC1CCCCC1
Reactant: Cc1sc2ccccc2c1Br
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCCCCC
Product: Cc1sc2ccccc2c1C(O)C1CCCCC1
Reaction time: 0.17 h
Yield: 85 %

Procedure:
3-Bromo-2-methyl-1-benzothiophene (2.00 g) synthesized above was dissolved in tetrahydrofuran (40 mL), 1.6M n-butyllithium hexane solution (6.63 mL) was added dropwise at −78° C. The mixture was stirred under a nitrogen atmosphere for 10 min, cyclohexanecarbaldehyde (2.50 mL) was added, and the mixture was stirred −78° C. for 30 min and at room temperature for 30 min. Saturated aqueous ammonium chloride solution was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=3:17, volume ratio) to give the title object compound (1.95 g, 85%) as a yellow oil.
Reaction SMILES: [CH3:1][N:2]([CH2:12][CH2:13][O:14][C:15]1[CH:22]=[CH:21][C:18]([CH:19]=O)=[CH:17][CH:16]=1)[C:3]1[S:4][C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=1.[S:23]1[CH2:27][C:26](=[O:28])[NH:25][C:24]1=[O:29].C([O-])(=O)C.[NH2+]1CCCCC1>C1(C)C=CC=CC=1>[CH3:1][N:2]([CH2:12][CH2:13][O:14][C:15]1[CH:22]=[CH:21][C:18]([CH:19]=[C:27]2[S:23][C:24](=[O:29])[NH:25][C:26]2=[O:28])=[CH:17][CH:16]=1)[C:3]1[S:4][C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=1
Reactant: CN(CCOc1ccc(C=O)cc1)c1nc2ccccc2s1
Reactant: O=C1CSC(=O)N1
Agent: C1CC[NH2+]CC1
Agent: CC(=O)[O-]
Solvent: Cc1ccccc1
Product: CN(CCOc1ccc(C=C2SC(=O)NC2=O)cc1)c1nc2ccccc2s1

Procedure:
A solution of 4-[2-(N-methyl-N-(2-benzothiazolyl)amino)ethoxy]benzaldehyde (1.9 g) and 2,4-thiazolidinedione (0.8 g) in toluene (100 ml) containing a catalytic quantity of piperidinium acetate was boiled under reflux in a Dean and Stark apparatus for 2 hours. The mixture was cooled and filtered and the filtered solid was dried to give the title compound (mp 219° C.).
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][CH:4]=1.[Br:11][C:12]1[CH:18]=[CH:17][C:15]([NH2:16])=[CH:14][CH:13]=1>>[Br:11][C:12]1[CH:18]=[CH:17][C:15]([NH:16][C:7]([C:6]2[CH:9]=[CH:10][C:3]([S:2][CH3:1])=[CH:4][CH:5]=2)=[NH:8])=[CH:14][CH:13]=1
Reactant: Nc1ccc(Br)cc1
Reactant: CSc1ccc(C#N)cc1
Product: CSc1ccc(C(=N)Nc2ccc(Br)cc2)cc1
Yield: 77.7 %

Procedure:
The title compound was prepared from 4-methylthiobenzonitrile (17.3 g, 116 mmol) and 4-bromoaniline (20 g, 116 mmol) by following the procedure described in preparation 10 (29 g, yield 77.7%, purity 99.8% by HPLC). MS m/z:321.1/323.2 (M+).
Reaction SMILES: [CH:1](=[N:8][CH2:9][P:10](=[O:21])([O:16][CH2:17][CH2:18][CH2:19][CH3:20])[O:11][CH2:12][CH2:13][CH2:14][CH3:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.Cl[C:28]([O:30][CH2:31][C:32]([C:34]1[CH:39]=[CH:38][C:37]([Br:40])=[CH:36][CH:35]=1)=[O:33])=[O:29]>O1CCCC1.CCCCCC>[CH:1](=[N:8][CH:9]([P:10]([O:16][CH2:17][CH2:18][CH2:19][CH3:20])([O:11][CH2:12][CH2:13][CH2:14][CH3:15])=[O:21])[C:28]([O:30][CH2:31][C:32]([C:34]1[CH:35]=[CH:36][C:37]([Br:40])=[CH:38][CH:39]=1)=[O:33])=[O:29])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCCCOP(=O)(CN=Cc1ccccc1)OCCCC
Reactant: O=C(Cl)OCC(=O)c1ccc(Br)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CCCCOP(=O)(OCCCC)C(N=Cc1ccccc1)C(=O)OCC(=O)c1ccc(Br)cc1
Reaction time: 0.5 h

Procedure:
Dibutyl N-benzylidene-aminomethylphosphonate (31.1 g) is dissolved in anhydrous tetrahydrofuran (500 ml) and the solution is cooled to -78° under a nitrogen atmosphere. Butyllithium (46 ml of a 2.2 M solution in hexane) is added over a period of 5 minutes. The resulting solution is stirred an additional 30 minutes at -78°, then treated dropwise over a period of 45 minutes with p-bromophenacyl chloroformate (13.9 g) in tetrahydrofuran (100 ml). The reaction mixture is stirred an additiona 2 hours at -78° followed by gradual warming to 3° over a period of 30 minutes. Evaporation of the solvent in vacuo leaves a gum which is partitioned between ether (500 ml) and 0.5 M pH 3 phosphate buffer (100 ml). The ethereal phase is separated, washed with water and saturated brine, dried over magnesium sulfate filtered, and evaporated in vacuo to an oil. Chromatographic purification of this material on silica gel gives p-bromophenacyl N-benzylidene-α-amino-dibutylphosphonoacetate.