Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:20]=[C:19]2[C:5]([C:6](=[O:22])[C:7](=[O:21])[C:8]3[S:18][CH2:17][C:11]4([CH2:16][CH2:15][NH:14][CH2:13][CH2:12]4)[O:10][C:9]=32)=[CH:4][CH:3]=1.[C:23]([C:27]1[CH:37]=[CH:36][C:30]([O:31][CH2:32][C@@H:33]2[CH2:35][O:34]2)=[CH:29][CH:28]=1)([CH3:26])([CH3:25])[CH3:24]>>[C:23]([C:27]1[CH:37]=[CH:36][C:30]([O:31][CH2:32][C@@H:33]([OH:34])[CH2:35][N:14]2[CH2:15][CH2:16][C:11]3([O:10][C:9]4[C:19]5[C:5]([C:6](=[O:22])[C:7](=[O:21])[C:8]=4[S:18][CH2:17]3)=[CH:4][CH:3]=[C:2]([Cl:1])[CH:20]=5)[CH2:12][CH2:13]2)=[CH:29][CH:28]=1)([CH3:24])([CH3:25])[CH3:26]
Reactant: O=C1C(=O)c2ccc(Cl)cc2C2=C1SCC1(CCNCC1)O2
Reactant: CC(C)(C)c1ccc(OC[C@@H]2CO2)cc1
Product: CC(C)(C)c1ccc(OC[C@@H](O)CN2CCC3(CC2)CSC2=C(O3)c3cc(Cl)ccc3C(=O)C2=O)cc1

Procedure:
Compound 192 was synthesized using 9-chlorospiro[naphtho[1,2-b][1,4]oxathiine-2,4′-piperidine]-5,6-dione, (2S)-2-[(4-tert-butylphenoxy)methyl]oxirane and conditions outlined in procedure Y. M.p.=94-97° C.; 400 MHz 1H NMR (DMSO-d6) δ: 7.89 (d, J=8.4 Hz, 1H), 7.67-7.62 (m, 2H), 7.28 (d, J=8.8 Hz, 2H), 6.85 (d, J=8.8 Hz, 2H), 4.86 (d, J=4.4 Hz, 1H), 4.0-3.92 (m, 2H), 3.87-3.83 (m, 1H), 3.08 (s, 2H), 2.84-2.75 (m, 2H), 2.48-2.41 (m, 4H), 2.02-1.94 (m, 2H), 1.86-1.76 (m, 2H), 1.25 (s, 9H); LCMS: 542 [M+H].
Reaction SMILES: [OH:1][C:2]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:3]=1[NH2:4].[Br:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]=[C:20]=[O:21])=[CH:15][CH:14]=1>>[OH:1][C:2]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:3]=1[NH:4][C:20]([NH:19][C:16]1[CH:17]=[CH:18][C:13]([Br:12])=[CH:14][CH:15]=1)=[O:21]
Reactant: Nc1ccc([N+](=O)[O-])cc1O
Reactant: O=C=Nc1ccc(Br)cc1
Product: O=C(Nc1ccc(Br)cc1)Nc1ccc([N+](=O)[O-])cc1O
Yield: 35.9 %

Procedure:
N-(2-Hydroxy-4-nitrophenyl)-N'-(4-bromo phenyl)urea was prepared from 2-hydroxy 4-nitro aniline (500 mg, 3.24 mmol) and 4-bromo phenyl isocyanate (3.24 mmol) according to the procedure in General Method B. The product was purified by dilution with methylene chloride and precipitation with hexanes. Filtering afforded the title compound(0.41 g, 37%). EI-MS m/z 352(M+H)+
Reaction SMILES: I.[C:2]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=N)SC.[CH3:19][NH:20][CH2:21][CH2:22][NH2:23].[C:24]([OH:31])(=[O:30])/[CH:25]=[CH:26]/[C:27]([OH:29])=[O:28]>C(O)C.CO>[C:24]([OH:31])(=[O:30])/[CH:25]=[CH:26]/[C:27]([OH:29])=[O:28].[CH3:19][N:20]1[CH2:21][CH2:22][NH:23][C:9]1=[N:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: CNCCN
Reactant: CSC(=N)Nc1ccccc1-c1ccccc1
Agent: I
Agent: O=C(O)/C=C/C(=O)O
Solvent: CCO
Solvent: CO
Product: CN1CCNC1=Nc1ccccc1-c1ccccc1

Procedure:
A mixture of 1-(2-biphenylyl)-2-methyl-2-thiopseudourea hydriodide (5.6 g) and N-methylethylenediamine (3.3 g) in ethanol (70 ml) was heated under reflux for 48 hours. Removal of the solvent gave an oil which was dissolved in methanol (25 ml) and treated with fumaric acid (1.7 g) to give 2-(1-methyl-2-imidazolidinylideneamino)biphenyl fumarate (m.p. 168°-169° C.) which was recrystallised from a 1:1 mixture of methanol and ether.
Reaction SMILES: [H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl[C:12]1[CH:13]=[CH:14][C:15]([N+:27]([O-:29])=[O:28])=[C:16]([N:18]([CH3:26])[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH:17]=1>CN(C)C=O>[CH2:3]([O:10][C:12]1[CH:13]=[CH:14][C:15]([N+:27]([O-:29])=[O:28])=[C:16]([N:18]([CH3:26])[C:19](=[O:25])[O:20][C:21]([CH3:22])([CH3:23])[CH3:24])[CH:17]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: OCc1ccccc1
Reactant: CN(C(=O)OC(C)(C)C)c1cc(Cl)ccc1[N+](=O)[O-]
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN(C(=O)OC(C)(C)C)c1cc(OCc2ccccc2)ccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 268.5 %

Procedure:
A mixture of sodium hydride (5.24 g, 55% dispersion in mineral oil), benzyl alcohol (13 g) and anhydrous N,N-dimethylformamide (150 ml) was stirred at room temperature for 30 minutes. To this mixture was added t-butyl N-(5-chloro-2-nitrophenyl)-N-methylcarbamate (8.7 g) at room temperature and this mixture was stirred for 18 hours. The reaction mixture was concentrated and the residue was partitioned between ethyl acetate and water. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated. The residue was chromatographed on a silica gel column using hexane: ethyl acetate=10:1 as the eluant to afford the title compound (29.2 g, yellow crystals, mp 108-110° C.).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:19]=[C:20]4[C:24](=[CH:25][CH:26]=3)[N:23]([CH2:27][C:28]3([NH:36]C(=O)OC(C)(C)C)[CH2:33][O:32]C(C)(C)[O:30][CH2:29]3)[CH2:22][CH2:21]4)[N:14]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH2:11][CH3:12])[CH3:2].CC1(C)OCC(NC(=O)OC(C)(C)C)(CNC2C=CC(CCCCCCCC)=CC=2)CO1>>[NH2:36][C:28]([CH2:27][N:23]1[C:24]2[C:20](=[CH:19][C:18]([C:15]3[N:14]=[C:13]([C:6]4[CH:7]=[CH:8][C:9]([O:10][CH2:11][CH3:12])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=4)[O:17][N:16]=3)=[CH:26][CH:25]=2)[CH2:21][CH2:22]1)([CH2:29][OH:30])[CH2:33][OH:32]
Reactant: CCOc1ccc(-c2nc(-c3ccc4c(c3)CCN4CC3(NC(=O)OC(C)(C)C)COC(C)(C)OC3)no2)cc1OCC
Agent: CCCCCCCCc1ccc(NCC2(NC(=O)OC(C)(C)C)COC(C)(C)OC2)cc1
Product: CCOc1ccc(-c2nc(-c3ccc4c(c3)CCN4CC(N)(CO)CO)no2)cc1OCC
Yield: 80 %

Procedure:
When the product of Step C was substituted for tert-butyl 2,2-dimethyl-5-((4-octylphenylamino)methyl)-1,3-dioxan-5-ylcarbamate in Example 1, Step B, the identical process afforded the title compound in 80% yield, as a creamy solid. 1H-NMR (DMSO-d6) 1.35 (m, 6H); 3.0 (tr, 2H, J=8.2 Hz); 3.17-3.29 (m, 2H+H2O); 3.42 (s, 2H); 3.55 (tr, 2H, J=8.2 Hz); 3.97 (s, 4H); 4.14 (m, 4H); 5.06 (broad s, 2H); 6.71 (d, 1H, J=8.4 Hz); 7.56 (m, 1H); 7.6-8.3 (m, 3H).
Reaction SMILES: C([Al:5]([CH2:10][CH:11]([CH3:13])[CH3:12])[CH2:6][CH:7]([CH3:9])[CH3:8])C(C)C.[C:14]1([OH:20])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C1(C)C=CC=CC=1>[O:20]([Al:5]([CH2:6][CH:7]([CH3:8])[CH3:9])[CH2:10][CH:11]([CH3:12])[CH3:13])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: CC(C)C[Al](CC(C)C)CC(C)C
Reactant: Oc1ccccc1
Solvent: Cc1ccccc1
Product: CC(C)C[Al](CC(C)C)Oc1ccccc1

Procedure:
In a manner analogous to that described in Example 1, triisobutylaluminum and phenol are reacted in absolute toluene to give phenoxy-diisobutylaluminum and this is then reacted with pyridine-N-oxide-2-thiol to give the title compound. The isolation of the product is carried out in an analogous manner. The yield of phenoxy-bis(2-pyridinethiolato)aluminum N,N'-dioxide, a white solid, is 98% of theory. Melting point: 240°-241° C. (with decomposition).
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([NH:12][CH2:13][CH2:14][O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH:6]=[CH:5]2.[N:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][NH2:29])[CH:23]=1>O1CCOCC1>[O:15]([CH2:14][CH2:13][NH:12][C:7]1[CH:6]=[CH:5][C:4]2[C:9](=[CH:10][CH:11]=[C:2]([NH:29][CH2:28][C:24]3[CH:23]=[N:22][CH:27]=[CH:26][CH:25]=3)[CH:3]=2)[N:8]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: Clc1ccc2nc(NCCOc3ccccc3)ccc2c1
Reactant: NCc1cccnc1
Solvent: C1COCCO1
Product: c1ccc(OCCNc2ccc3cc(NCc4cccnc4)ccc3n2)cc1
Temperature: 115 °C
Reaction time: 16 h

Procedure:
(6-Chloro-quinolin-2-yl)-(2-phenoxy-ethyl)-amine (150 mg, 0.503 mmol) was dissolved in 2 mL dioxane. Argon was bubbled through the solution for 2 minutes to remove oxygen. 3-Picolylamine (165 mg, 1.53 mmol), sodium tert.-butylate (119 mg, 1.24 mmol) and 1,1′-2-(dimethylamino)ferrocen-1-yl-palladium(II) chloride dinorbornylphosphine (16 mg, 0.03 mmol) were added. The reaction mixture was stirred in a sealed tube at 115° C. for 16 h. The solvent was evaporated and the residue purified by flash chromatography on silica gel (dichloromethane/methanol 100:0->90:10 gradient). The title compound was obtained as a light brown solid (108 mg, 58%), MS: m/e=371.1 (M+H+).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:12]([NH:13][C:14](=[O:18])OCC)=[N:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH3:19])[CH:9]=2)[N:4]=1.[Cl:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1>>[CH3:1][O:2][C:3]1[C:12]([NH:13][C:14]([N:30]2[CH2:29][CH2:28][N:27]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[Cl:20])[CH2:32][CH2:31]2)=[O:18])=[N:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH3:19])[CH:9]=2)[N:4]=1
Reactant: CCOC(=O)Nc1nc2cc(C)ccc2nc1OC
Reactant: Clc1ccccc1N1CCNCC1
Product: COc1nc2ccc(C)cc2nc1NC(=O)N1CCN(c2ccccc2Cl)CC1
Yield: 66 %

Procedure:
Ethyl N-(2-methoxy-6-methylquinoxalin-3-yl)carbamate and 1-(2-chlorophenyl)piperazine were reacted by the same way with the example 43 to obtain the titled compound (yield, 66%). 1H NMR (300 MHz, CDCl3): δ 2.43-2.49 (m, 3H), 3.10-3.15 (m, 4H), 3.81 (s, 3H), 3.08-4.12 (m, 4H), 7.00-7.12 (m, 3H), 7.24-7.40 (m, 3H), 7.49-7.65 (m, 2H).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH3:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[C:19]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)=[N:18][C:17]([OH:28])=[N:16]2)=[CH:11][CH:10]=1.[F:29][C:30]([F:34])([F:33])[CH2:31]I.C(OCC)(=O)C>CN(C)C=O.O>[CH3:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([N:15]2[C:19]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)=[N:18][C:17]([O:28][CH2:31][C:30]([F:34])([F:33])[F:29])=[N:16]2)=[CH:13][CH:14]=1
Reactant: COc1ccc(-c2nc(O)nn2-c2ccc(OC)cc2)cc1
Reactant: FC(F)(F)CI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COc1ccc(-c2nc(OCC(F)(F)F)nn2-c2ccc(OC)cc2)cc1
Temperature: 100 °C
Reaction time: 0.17 h
Yield: 53.5 %

Procedure:
Potassium carbonate (697 mg, 5.05 mmol) was added to a solution of 1,5-bis(4-methoxyphenyl)-1H-1,2,4-triazol-3-ol (0.3 g, 1.01 mmol) in dimethylformamide (3 mL). After 10 minute stirring, 2,2,2-trifluoroethyl iodide (0.497 mL, 5.05 mmol) was added to the mixture and the mixture was heated at 100° C. for 3 hours. After cooling, 100 mL of ethyl acetate and 20 mL of water were poured into the mixture. The organic layer was separated, washed with water and brine, and dried over magnesium sulfate. The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate 10:1-5:1). The desired product was triturated with hexane, isolated by filtartion, and dried in vacuo to give 1,5-bis(4-methoxyphenyl)-3-(2,2,2-trifluoroethoxy)-1H-1,2,4-triazole (205 mg, 53.6%).
Reaction SMILES: [CH:1]1([CH:7]([C:18]2[CH:22]=[C:21]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)[O:20][C:19]=2[CH3:33])[O:8][C:9]2[CH:17]=[CH:16][C:12]([C:13](O)=[O:14])=[CH:11][CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:34][NH:35][CH2:36][CH2:37][C:38]([O:40]CC)=[O:39]>>[CH:1]1([CH:7]([C:18]2[CH:22]=[C:21]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:30])[F:31])=[CH:25][CH:24]=3)[O:20][C:19]=2[CH3:33])[O:8][C:9]2[CH:10]=[CH:11][C:12]([C:13]([N:35]([CH3:34])[CH2:36][CH2:37][C:38]([OH:40])=[O:39])=[O:14])=[CH:16][CH:17]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CCOC(=O)CCNC
Reactant: Cc1oc(-c2ccc(C(F)(F)F)cc2)cc1C(Oc1ccc(C(=O)O)cc1)C1CCCCC1
Product: Cc1oc(-c2ccc(C(F)(F)F)cc2)cc1C(Oc1ccc(C(=O)N(C)CCC(=O)O)cc1)C1CCCCC1
Yield: 88.3 %

Procedure:
An operation similar to that in Example 1 (4) was performed using 4-(cyclohexyl{2-methyl-5-[4-(trifluoromethyl)phenyl]-3-furyl}methoxy)benzoic acid (128 mg) as well as ethyl 3-(methylamino)propanoate (45 mg) to give the title compound (134 mg, 88%) as an amorphous compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([OH:13])=[C:8]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:7]([CH3:20])=[CH:6]2.[H-].[Na+].F[C:24]1[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][CH:25]=1>CN(C=O)C>[CH3:20][C:7]1[C:8]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[C:9]([O:13][C:24]2[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][CH:25]=2)[C:10]2[C:5]([CH:6]=1)=[CH:4][C:3]([O:2][CH3:1])=[CH:12][CH:11]=2
Reactant: COc1ccc2c(O)c(-c3ccccc3)c(C)cc2c1
Reactant: O=[N+]([O-])c1ccc(F)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc2c(Oc3ccc([N+](=O)[O-])cc3)c(-c3ccccc3)c(C)cc2c1
Temperature: 0 °C
Yield: 78.5 %

Procedure:
Compound 7 (428 mg, 1.62 mmol, 1 equiv) was dissolved in DMF (5 mL) and cooled to 0° C. under N2. Sodium hydride, 60% dispersion (71 mg, 1.78 mmol, 1.1 equiv), followed by 1-fluoro-4-nitrobenzene (457 mg, 3.24 mmol, 2 equiv) were added and the entire reaction mixture was heated to 70° C. for 18 h. The mixture was then partitioned between EtOAc (50 mL) and H2O (50 mL). The organic layer was washed with saturated aqueous NaCl (100 mL), dried over Na2SO4, filtered and concentrated to dryness. The residue was purified by silica gel flash column chomatography (5% EtOAc in hexanes) to provide 28 (490 mg, 78%) as a clear oil. 1HNMR (400 MHz, DMSO-d6): δ 8.03 (m, 2H), 7.76 (s, 1H), 7.53 (m, 1H), 7.38-7.08 (m, 7H), 6.78 (m, 2H), 3.87 (s, 3H), 2.18 (s, 3H). MS m/z 473.3 (M+H)+.
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH2:8]([S:10]([N:13]1[CH2:18][CH2:17][CH:16]([C:19]2[C:27]3[C:22](=[C:23]([C:43]([NH2:45])=[O:44])[CH:24]=[C:25]([C:28]4[CH:33]=[C:32]([CH2:34][NH:35][CH2:36][C@@H:37]5[CH2:41]CCO5)[CH:31]=[C:30]([F:42])[CH:29]=4)[CH:26]=3)[NH:21][CH:20]=2)[CH2:15][CH2:14]1)(=[O:12])=[O:11])[CH3:9].O1CC[CH2:48][C@H:47]1CN>>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH2:8]([S:10]([N:13]1[CH2:14][CH2:15][CH:16]([C:19]2[C:27]3[C:22](=[C:23]([C:43]([NH2:45])=[O:44])[CH:24]=[C:25]([C:28]4[CH:33]=[C:32]([CH2:34][NH:35][CH2:36][CH:37]([CH3:41])[CH2:47][CH3:48])[CH:31]=[C:30]([F:42])[CH:29]=4)[CH:26]=3)[NH:21][CH:20]=2)[CH2:17][CH2:18]1)(=[O:12])=[O:11])[CH3:9]
Reactant: NC[C@@H]1CCCO1
Reactant: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4cc(F)cc(CNC[C@@H]5CCCO5)c4)cc23)CC1
Solvent: O=C(O)C(F)(F)F
Product: CCC(C)CNCc1cc(F)cc(-c2cc(C(N)=O)c3[nH]cc(C4CCN(S(=O)(=O)CC)CC4)c3c2)c1
Yield: 54.5 %

Procedure:
The title compound was prepared according to the general procedure of 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-[3-fluoro-5-({[(2S)-tetrahydro-2-furanylmethyl]amino}methyl)phenyl]-1H-indole-7-carboxamide trifluoroacetate, substituting 2-methyl-1-butanamine (45 mg, 0.525 mmol) for 1-[(2S)-tetrahydro-2-furanyl]methanamine to afford 30.5 mg of the title compound (54.5%).
Reaction SMILES: [CH2:1]([C:3]1[CH:4]=[C:5]([CH2:9][CH2:10][C:11]2[O:15][C:14]([CH3:16])=[N:13][C:12]=2[C:17]([OH:19])=O)[CH:6]=[CH:7][CH:8]=1)[CH3:2]>S(Cl)(Cl)=O>[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]2[C:17](=[O:19])[C:12]3[N:13]=[C:14]([CH3:16])[O:15][C:11]=3[CH2:10][CH2:9][C:5]=2[CH:4]=1)[CH3:2]
Reactant: CCc1cccc(CCc2oc(C)nc2C(=O)O)c1
Solvent: O=S(Cl)Cl
Product: CCc1ccc2c(c1)CCc1oc(C)nc1C2=O

Procedure:
A solution of the product from step (vii) (9.5 g) in thionyl chloride (100 ml) was stirred at room temperature for 4 days. After removal of solvent under reduced pressure, the residue was dissolved in 1,2-dichloroethane (200 ml) and treated with aluminium chloride (23 g). The reaction mixture was heated at reflux for 1 hour and allowed to cool. The resultant suspension was partitioned between 10% hydrochloric acid and dichloromethane. The combined extracts were evaporated, triturated with acetonitrile, and filtered through a plug of celite. Evaporation afforded a residue which was purified by chromatography eluting with 50-100% ethyl acetate in isohexane.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[OH:11].N1C=CC=CC=1.[C:18](Cl)(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C1COCC1>[C:18]([NH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[OH:11])(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: Nc1ccc(C(=O)O)cc1O
Solvent: c1ccncc1
Solvent: C1CCOC1
Product: O=C(O)c1ccc(NC(=O)c2ccccc2)c(O)c1
Reaction time: 0.08 h
Yield: 78.6 %

Procedure:
To a suspension of 4-amino-3-hydroxybenzoic acid (7.66 g, 50.0 mmol) in THF (100 mL) was added pyridine (4.3 mL, 53.2 mmol, 1.06 eq) followed by benzoyl chloride (6.1 mL, 52.6 mmol, 1.05 eq) at 0° C. After 5 min, the reaction was quenched with H2O then extracted with CH2Cl2 (4×80 mL). Crude product precipitated out of organic layer then was collected by filtration to afford 4-benzamido-3-hydroxybenzoic acid (10.1 g, 39.3 mmol, 79%). The product was carried over to next step without further purification.
Reaction SMILES: [CH3:1][N:2]([CH2:4][CH2:5][CH:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7]1)[CH3:3].CN(CCC1CC=CC=1)C.[Cl-:25].[Cl-].[Cl-].[CH:28]1([Zr+3:33])[CH:32]=[CH:31][CH:30]=[CH:29]1.[Cl-].[Cl-].[Cl-].C[Zr](C)(C)(C)(C)C1C=CC=C1>>[Cl-:25].[Cl-:25].[CH3:1][N:2]([CH2:4][CH2:5][CH:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[C:7]1[Zr+2:33][CH:28]1[CH:32]=[CH:31][CH:30]=[CH:29]1)[CH3:3]
Reactant: [Zr+3]C1C=CC=C1
Reactant: CN(C)CCC1C=Cc2ccccc21
Agent: C[Zr](C)(C)(C)(C)C1C=CC=C1
Agent: CN(C)CCC1=CC=CC1
Agent: [Cl-]
Product: CN(C)CCC1C([Zr+2]C2C=CC=C2)=Cc2ccccc21
Yield: 35 %

Procedure:
Example 1 was repeated in the same manner as described except that 1-(N,N-dimethylaminoethyl)indene was substituted for (N,N-dimethylaminoethyl)cyclopentadiene and that cyclopentadienylzirconium trichloride was substituted for pentamethylcyclopentadienylzirconium trichloride. The yield was 35.0%. The physical properties of the product are as follows:
Reaction SMILES: [OH:1][C:2]1[C:3]([I:12])=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH:5]=O.C(=O)([O-])[O-].[K+].[K+].C(OP([CH2:27][C:28]([O:30][CH3:31])=[O:29])(OCC)=O)C>CO>[OH:1][C:2]1[C:3]([I:12])=[C:4](/[CH:5]=[CH:27]/[C:28]([O:30][CH3:31])=[O:29])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11]
Reactant: COc1ccc(C=O)c(I)c1O
Reactant: CCOP(=O)(CC(=O)OC)OCC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: COC(=O)/C=C/c1ccc(OC)c(O)c1I
Temperature: 55 °C
Reaction time: 8 h

Procedure:
To a solution of 3-hydroxy-2-iodo-4-methoxybenzaldehyde (2.5 g, 8.99 mmol) in methanol (30 ml) was added potassium carbonate (3.11 g, 22.48 mmol) and methyl diethylphosphonoacetate (1.980 ml, 10.79 mmol). The initial cloudy mixture became clear with the addition of the base (although the base itself was mostly insoluble) The mixture was stirred overnight at 55° C. and became yellow and cloudy again. The solution was then concentrated in vacuo and the residue was taken up in ethyl acetate (20 mL) and 1M HCl (aq) (20 mL). The organic layer was separated and washed with brine (1×20 mL), dried over sodium sulfate, concentrated in vacuo, and purified via column chromatography on a Biotage 65i column eluting with 0% ethyl acetate in hexanes (1 CV) followed by a gradient to 50% ethyl acetate in hexanes (over 7 CV) to furnish the desired product as the E olefin. 1H NMR (CDCl3, 500 MHz) $ 7.95 (d, J=15.9 Hz, 1H), 7.14 (d, J=8.4 Hz, 1H), 6.74 (d, J=8.6 Hz, 1H), 6.27 (d, J=15.8 Hz, 1H), 3.91 (s, 3H), 3.80 (s, 3H), 2.34 (s, 3H).
Reaction SMILES: [F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]=[C:7]2[CH3:12].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][NH:6][CH:7]2[CH3:12]
Reactant: CC1=NCCc2c(F)cccc21
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Product: CC1NCCc2c(F)cccc21

Procedure:
In close analogy to the procedure described above, 5-fluoro-1-methyl-3,4-dihydro-isoquinoline is reacted with sodium triacetoxyborohydride to provide the title compound.
Reaction SMILES: B([O-])([O-])O[C:3]1[CH:8]=[CH:7][C:6]([O:9][CH2:10][CH3:11])=[C:5]([F:12])[CH:4]=1.Br[C:16]1[CH:17]=[CH:18][C:19]2[N:25]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:24][CH2:23][C:22]([C:33]([O:35][CH3:36])=[O:34])=[CH:21][C:20]=2[CH:37]=1.C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:29]([O:28][C:26]([N:25]1[C:19]2[CH:18]=[CH:17][C:16]([C:3]3[CH:8]=[CH:7][C:6]([O:9][CH2:10][CH3:11])=[C:5]([F:12])[CH:4]=3)=[CH:37][C:20]=2[CH:21]=[C:22]([C:33]([O:35][CH3:36])=[O:34])[CH2:23][CH2:24]1)=[O:27])([CH3:32])([CH3:31])[CH3:30]
Reactant: CCOc1ccc(OB([O-])[O-])cc1F
Reactant: COC(=O)C1=Cc2cc(Br)ccc2N(C(=O)OC(C)(C)C)CC1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Product: CCOc1ccc(-c2ccc3c(c2)C=C(C(=O)OC)CCN3C(=O)OC(C)(C)C)cc1F
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
In a mixture of water:ethanol toluene (1:1:10, v/v, 42.0 ml) were dissolved 4-ethoxy-3-fluorophenyl borate (754 mg) and methyl 7-bromo-1-(t-butoxycarbonyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate (1305 mg). To the solution was added potassium carbonate (1132 mg), and the mixture was stirred under argon atmosphere at room temperature for 30 minutes. To the mixture was added tetrakistriphenylphosphinepalladium (158 mg), and the mixture was heated to reflux under argon atmosphere for 10 hours. The mixture was diluted with ethyl acetate, and washed with water and saturated brine, and the organic layer was dried with anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified with silica gel column chromatography (75 g, hexane:ethyl acetate=4:1) to give methyl 1-(t-butoxycarbonyl)-7-(4-ethoxy-3-fluorophenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate as yellow amorphous. The obtained methyl 1-(t-butoxycarbonyl)-7-(4-ethoxy-3-fluorophenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate was dissolved in ethyl acetate (80 ml). To the solution was added 1N hydrochloric acid (15 ml) at room temperature, and the mixture was stirred at 100° C. for 1 hour and neutralized with 1N sodium hydroxide and saturated sodium hydrogen carbonate solution. To the mixture was added ethyl acetate, and the separated organic layer was washed with saturated sodium hydrogen carbonate solution, water and saturated brine, and dried with anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified with silica gel column chromatography (50 g, hexane:ethyl acetate=9:1→4:1→2:1) to give methyl 7-(4-ethoxy-3-fluorophenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate (1007 mg, 86%) as yellow crystals.
Reaction SMILES: C[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-:10])=[O:9])[C:3]=1[CH2:11][N:12]1[C:16](=[O:17])[C:15]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:14]2[C:13]1=[O:22].CC1C([N+]([O-])=O)=CC=CC=1C[N:34]1[C:38](=[O:39])C2=CC=CC=C2C1=O>>[C:38]([C:7]1[CH:6]=[CH:5][C:4]([N+:8]([O-:10])=[O:9])=[C:3]([CH2:11][N:12]2[C:13](=[O:22])[C:14]3=[CH:21][CH:20]=[CH:19][CH:18]=[C:15]3[C:16]2=[O:17])[CH:2]=1)(=[O:39])[NH2:34]
Reactant: Cc1c(CN2C(=O)c3ccccc3C2=O)cccc1[N+](=O)[O-]
Reactant: Cc1cccc([N+](=O)[O-])c1CN1C(=O)c2ccccc2C1=O
Product: NC(=O)c1ccc([N+](=O)[O-])c(CN2C(=O)c3ccccc3C2=O)c1

Procedure:
N-(2-methyl-6-nitrophenyl)methyl-phthalimide, mixed with N-(2-methyl-3-nitrophenyl)methyl-phthalimide. M.p. 100°-124° C.