Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=[O:9])=[CH:6][CH:5]=1)=[N+:2]=[N-:3].[C:13]([C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][N:16]=1)#[CH:14]>O1CCOCC1.O.CCOC(C)=O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2]>[NH:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:15]([C:13]2[N:3]=[N:2][N:1]([C:4]3[CH:5]=[CH:6][C:7]([C:8]([OH:10])=[O:9])=[CH:11][CH:12]=3)[CH:14]=2)=[N:16]1
Reactant: [N-]=[N+]=Nc1ccc(C(=O)O)cc1
Reactant: C#Cc1n[nH]c2ccccc12
Agent: [Cu+2]
Agent: O=S(=O)([O-])[O-]
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Solvent: O
Product: O=C(O)c1ccc(-n2cc(-c3n[nH]c4ccccc34)nn2)cc1
Reaction time: 48 h
Yield: 106 %

Procedure:
4-azidobenzoic acid (252 mg; 1.55 mmol; 1.1 eq.) and 3-ethynyl-1H-indazole (200 mg; 1.4 mmol; 1.0 eq.) were dissolved in 1,4-dioxane (3 mL). D-(−)-isoascorbic acid sodium salt (28 mg; 0.14 mmol; 0.1 eq.) followed by a solution of copper sulfate pentahydrate (7 mg; 0.03 mmol; 0.02 eq.) in water (0.75 mL) were added and the reaction mixture was stirred at 900 for 48 h. Reaction mixture was diluted with EtOAc and extracted with a NaOH (0.1N). Aqueous phase was filtered, acidified to pH 4-5 by addition of HCl (5N) and the precipitate thus obtained, was filtered, washed with water and dried under reduced pressure at 50° C. to afford the title compound as a white solid (453 mg, 100%). 1H NMR (300 MHz, DMSO-d6) δ 13.53 (s, 1H), 9.57 (s, 1H), 8.49 (d, J=8.1 Hz, 1H), 8.42-8.24 (m, 3H), 8.13-8.03 (m, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.63-7.50 (m, 1H), 7.45-7.29 (m, 2H).
Reaction SMILES: [OH:1][CH2:2][C:3]1[C:4]([C:11]2[NH:12][CH:13]=[CH:14][N:15]=2)=[C:5]([OH:10])[C:6]([CH3:9])=[N:7][CH:8]=1.CI.[C:18]([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[OH:1][CH2:2][C:3]1[C:4]([C:11]2[N:15]([CH3:18])[CH:14]=[CH:13][N:12]=2)=[C:5]([OH:10])[C:6]([CH3:9])=[N:7][CH:8]=1
Reactant: Cc1ncc(CO)c(-c2ncc[nH]2)c1O
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Solvent: O
Product: Cc1ncc(CO)c(-c2nccn2C)c1O
Reaction time: 19 h

Procedure:
5-(hydroxymethyl)-4-(1H-imidazol-2-yl)-2-methylpyridin-3-ol (1.03 g, 5.0 mmol) was suspended in DMF (50 mL) and methyl iodide (0.31 mL, 5 mmol) was added at rt. The reaction mixture was stirred over a period of 19 h and a further portion of methyl iodide (0.125 mL, 2 mmol) was added and stirred over a period of 23 h. Aq. K2CO3 solution (10 mL) and water (50 mL) was added and extracted with ethyl acetate (2×50 mL). Combined organic layers were dried over MgSO4 (10 g) and evaporated to a volume of 20 mL. After 3 days at room temperature, the crystallized product was filtered off and dried to give (600 mg) the title compound as a light beige solid.
Reaction SMILES: [C:1]([C:3]1[N:7]=[CH:6][NH:5][N:4]=1)#[N:2].C(O[C@@H:12]1[O:24][C@H:23]([CH2:25][O:26][C:27](=[O:29])[CH3:28])[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:13]1[O:14][C:15](=[O:17])[CH3:16])(=O)C.P([O-])(OC1C=CC([N+]([O-])=O)=CC=1)(OC1C=CC([N+]([O-])=O)=CC=1)=O>C(Cl)(Cl)Cl>[C:1]([C:3]1[N:7]=[CH:6][N:5]([C@@H:12]2[O:24][C@H:23]([CH2:25][O:26][C:27](=[O:29])[CH3:28])[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:13]2[O:14][C:15](=[O:17])[CH3:16])[N:4]=1)#[N:2]
Reactant: CC(=O)OC[C@H]1O[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: N#Cc1nc[nH]n1
Agent: O=[N+]([O-])c1ccc(OP(=O)([O-])Oc2ccc([N+](=O)[O-])cc2)cc1
Solvent: ClC(Cl)Cl
Product: CC(=O)OC[C@H]1O[C@@H](n2cnc(C#N)n2)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Reaction time: 0.25 h

Procedure:
A mixture of 3-cyano-1,2,4-triazole (9.41 g., 0.10 mol) and 1,2,3,5-tetra-O-acetyl-β -D-ribofuranose (31.8 g., 0.10 mol) was heated in an oil bath maintained at 150°. Bis(p-nitrophenyl) phosphate (100 mg.) was added with stirring and heating at 150° under diminished pressure was continued for 15 min. The residue was dissolved in chloroform, the solution was filtered and the solvent was removed. Crystallization of the residue from ether provided 28.2 g. (80%) of product with M.P. 96-97°.
Reaction SMILES: C1(C[C@H](N[C:18](=[O:30])[C@H:19]([CH2:24][C:25]2[N:26]=[CH:27][S:28][CH:29]=2)[CH2:20][C:21]([OH:23])=[O:22])[C@@H](O)[C@@H](O)CC(C)C)CCCCC1.[O:31]1CCNC1=O.[OH-].[Li+].OO>>[S:28]1[CH:29]=[C:25]([CH2:24][C@H:19]([CH2:20][C:21]([OH:23])=[O:22])[C:18]([OH:30])=[O:31])[N:26]=[CH:27]1
Reactant: O=C1NCCO1
Reactant: CC(C)C[C@H](O)[C@H](O)[C@H](CC1CCCCC1)NC(=O)[C@@H](CC(=O)O)Cc1cscn1
Agent: OO
Agent: [Li+]
Agent: [OH-]
Product: O=C(O)C[C@@H](Cc1cscn1)C(=O)O

Procedure:
4-{[1(S)-(Cyclohexylmethyl)-2(R),3(S)-dihydroxy-5-methylhexyl]amino}-4-oxo-3(R)-(4-thiazolylmethyl)butanoic Acid: The desired 2-oxazolidinone of the previous section (4.02 g, 10.5 mmol) was reacted with lithium hydroxide-hydrogen peroxide according to the procedure of section C(g) of this example to give the monoprotected dicarboxylic acid of formula 2, i.e. the 4-tertbutyl ester of 2(R)-(4-thiazolylmethyl)butanedioic acid. Subsequent coupling of the latter compound (2.83 g, 10.4 mmol) with 2(S)-amino-1-cyclohexyl-6-methyl-3(R),4(S)-heptanediol hydrochloride (3.21 g, 11.5 mmol) according to the coupling procedure section C(g) of this example gave the desired protected amido acid of formula 3 wherein W1 is tert-butoxy, R2 is 4-thiazolylmethyl and B is 1(S)-(cyclohexylmethyl)-2(R),3(S)-dihydroxy-5-methylhexyl, as a white solid (3.75 g, 72%); 1H NMR (CDCl3) δ8.70 (s, 1H), 7.10 (s,1H), 5.96 (d, J=8.3 Hz, 1H), 4.40-4.25 (m,2H), 3.40-2.70 (m,6H), 2.40 (dd, J=4.4 Hz,16.8 Hz, 1H), 1.95-1.10 (m, 17H), 1.40 (s,9H), 0.90 (d, J=6.6 Hz, 3H), 0.80 (d, J=6.4 Hz, 3H). The latter compound was deprotected as follows: The compound (3.7 g, 7.45 mmol) was dissolved in CH2Cl2 (30 mL). Under a N2 atmosphere at 0°, TFA (6 mL) was added to the solution. The reaction mixture was stirred for 5.5 h. At this point, another portion of TFA (6 mL) was added to the reaction mixture at 0°. The mixture was stirred at room temperature for 3 h. Thereafter, the mixture was diluted with Et2O and concentrated to dryness under reduced pressure to give the desired amido acid (4.70 g); FAB mass spectrum, m/z: 441 (M+H)+. The compound was used without further purification for ensuing coupling steps.
Reaction SMILES: [C:1]([O:10]CC)(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4].[OH-].[CH2:14]([N+:18]([CH2:27][CH2:28][CH2:29][CH3:30])([CH2:23][CH2:24][CH2:25][CH3:26])[CH2:19][CH2:20][CH2:21][CH3:22])[CH2:15][CH2:16][CH3:17]>O>[C:1]([O-:10])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4].[CH2:27]([N+:18]([CH2:14][CH2:15][CH2:16][CH3:17])([CH2:19][CH2:20][CH2:21][CH3:22])[CH2:23][CH2:24][CH2:25][CH3:26])[CH2:28][CH2:29][CH3:30]
Reactant: CCOC(=O)c1ccccc1O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [OH-]
Solvent: O
Product: O=C([O-])c1ccccc1O
Temperature: 60 °C

Procedure:
A glass flask with reflux condenser, heatable oil bath, mechanical stirrer and internal thermometer was charged at room temperature with 35.90 g of ethyl salicylate and 282.13 g of water and these components were stirred together thoroughly. Subsequently 139.98 g of tetrabutylammonium hydroxide (40% strength in water) were added and the reaction mixture was heated to 60° C. It was stirred at 60° C. for one hour (the contents of the flask became clear). Then the reaction mixture was cooled and the water was distilled off under reduced pressure, 20 mbar, at 30-45° C. The residue was taken up at 60° C. in 200 ml of toluene. Subsequently the mixture was redistilled. The residue was recrystallized from 50 ml of butyl acetate. The product was filtered off, washed with butyl acetate and dried at 80° C. and 10 mbar in a vacuum drying cabinet. This gave a white solid.
Reaction SMILES: [NH2:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][N:5]=[C:4]([O:11][C:12]2[CH:13]=[C:14]([CH:19]=[CH:20][CH:21]=2)[C:15]([O:17][CH3:18])=[O:16])[CH:3]=1>CO.[Pd]>[NH2:1][C:2]1[C:7]([NH2:8])=[CH:6][N:5]=[C:4]([O:11][C:12]2[CH:13]=[C:14]([CH:19]=[CH:20][CH:21]=2)[C:15]([O:17][CH3:18])=[O:16])[CH:3]=1
Reactant: COC(=O)c1cccc(Oc2cc(N)c([N+](=O)[O-])cn2)c1
Agent: [Pd]
Solvent: CO
Product: COC(=O)c1cccc(Oc2cc(N)c(N)cn2)c1
Reaction time: 36 h

Procedure:
To a solution of the product of Step 2 in MeOH (180 mL) and EtOAC (50 mL), was added 10% palladium on carbon (280 mg). This mixture was then stirred under hydrogen atmosphere for 36 h. The reaction mixture was filtered and then concentrated to afford the title compound, which was used directly to next step without further purification. MS (ES+) m/e 260 [M+H]+.
Reaction SMILES: [Li][CH2:2]CCC.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CI.[Br:27][C:28]1[CH:29]=[C:30]2[C:35](=[CH:36][CH:37]=1)[O:34][CH:33]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[CH2:32][C:31]2=O>C1COCC1>[Br:27][C:28]1[CH:29]=[C:30]2[C:35](=[CH:36][CH:37]=1)[O:34][CH:33]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[CH2:32][C:31]2=[CH2:2]
Reactant: [Li]CCCC
Reactant: O=C1CC(c2ccccc2)Oc2ccc(Br)cc21
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CI
Solvent: C1CCOC1
Product: C=C1CC(c2ccccc2)Oc2ccc(Br)cc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 20 %

Procedure:
A solution of n-BuLi (2.5 M, 3.80 mL) was added to a mixture of PPh3•MeI. (4.092 g, 10.13 mmol) in THF at −10° C. The mixture was stirred for 1 h at the same temperature, and then 6-bromo-2-phenylchroman-4-one (2 g, 6.62 mmol) was added. The mixture was allowed to warm to room temperature and stirred for 3 h. The resulting mixture was concentrated and purified by column chromatography to give 6-bromo-4-methylene-2-phenylchroman (400 mg, 20%). 1H-NMR (CDCl3): 2.76 (m, 2H), 4.90 (d, 1H), 5.01 (m, 1H), 5.48 (d, 1H), 6.76 (d, 1H), 7.31 (m, 6H), 7.62 (d, 1H).
Reaction SMILES: ClS(C1C=CC(C(O)=O)=CC=1)(=O)=O.[Cl:14][C:15]1[CH:21]=[CH:20][C:18]([NH2:19])=[CH:17][C:16]=1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1.[F:28][C:29]([F:45])([F:44])[CH2:30][NH:31][S:32]([C:35]1[CH:43]=[CH:42][C:38]([C:39](O)=[O:40])=[CH:37][CH:36]=1)(=[O:34])=[O:33]>FC(F)(F)CN>[Cl:14][C:15]1[CH:21]=[CH:20][C:18]([NH:19][C:39](=[O:40])[C:38]2[CH:42]=[CH:43][C:35]([S:32](=[O:33])(=[O:34])[NH:31][CH2:30][C:29]([F:28])([F:44])[F:45])=[CH:36][CH:37]=2)=[CH:17][C:16]=1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1
Reactant: Nc1ccc(Cl)c(-c2ccccn2)c1
Reactant: O=C(O)c1ccc(S(=O)(=O)NCC(F)(F)F)cc1
Agent: NCC(F)(F)F
Agent: O=C(O)c1ccc(S(=O)(=O)Cl)cc1
Product: O=C(Nc1ccc(Cl)c(-c2ccccn2)c1)c1ccc(S(=O)(=O)NCC(F)(F)F)cc1

Procedure:
1 g of 4-(chlorosulfonyl)benzoic acid was reacted with 500 μL of 2,2,2-trifluoroethanamine via Procedure H. 60 mg of 4-chloro-3-(pyridin-2-yl)aniline was coupled to 92 mg of 4-(N-(2,2,2-trifluoroethyl)sulfamoyl)benzoic acid by Procedure G and purified by reverse phase HPLC to yield N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(N-(2,2,2-trifluoroethyl)sulfamoyl)benzamide. MS (Q1) 470 (M)+.
Reaction SMILES: [CH:1]([CH:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([CH:14]3[CH2:16][CH:15]3[C:17]3[CH:18]=[C:19]4[C:24](=[CH:25][CH:26]=3)[CH:23]=[C:22]([C:27]#[N:28])[CH:21]=[CH:20]4)[CH:12]=2)[CH2:7][CH2:6][NH:5]1)([CH3:3])[CH3:2].[CH:29]1([CH:32]=O)[CH2:31][CH2:30]1.C([BH3-])#N.[Na+].O>CO>[CH:29]1([CH2:32][N:5]2[CH2:6][CH2:7][C:8]3[C:13](=[CH:12][C:11]([CH:14]4[CH2:16][CH:15]4[C:17]4[CH:18]=[C:19]5[C:24](=[CH:25][CH:26]=4)[CH:23]=[C:22]([C:27]#[N:28])[CH:21]=[CH:20]5)=[CH:10][CH:9]=3)[CH:4]2[CH:1]([CH3:3])[CH3:2])[CH2:31][CH2:30]1
Reactant: CC(C)C1NCCc2ccc(C3CC3c3ccc4cc(C#N)ccc4c3)cc21
Reactant: O=CC1CC1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CC(C)C1c2cc(C3CC3c3ccc4cc(C#N)ccc4c3)ccc2CCN1CC1CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of Example 20A (0.25 g, 0.95 mmol), cyclopropanecarboxaldehyde (71 mL, 0.95 mmol), and sodium cyanoborohydride (119 mg, 1.86 mmol), in methanol (3.5 mL) was heated to 50° C., stirred for 2 hours, cooled to room temperature, and treated with water. The resulting precipitate was collected by filtration, dried, and purified by flash column chromatography with 30% ethyl acetate/hexanes to provide the desired product.
Reaction SMILES: [F:1][C:2]([F:14])([F:13])[S:3]([C:6]1[CH:12]=[CH:11][C:9]([NH2:10])=[CH:8][CH:7]=1)(=[O:5])=[O:4].C(N(CC)CC)C.[Cl-].ClC1N(C)CC[NH+]1C.[CH3:31][O:32][C:33]1[C:34](=[O:57])[C:35]([CH3:56])=[C:36]([CH2:42][C:43]2[C:44]([O:52][C:53](=[O:55])[CH3:54])=[C:45]([CH:49]=[CH:50][CH:51]=2)[C:46](O)=[O:47])[C:37](=[O:41])[C:38]=1[O:39][CH3:40]>C(Cl)Cl>[CH3:31][O:32][C:33]1[C:34](=[O:57])[C:35]([CH3:56])=[C:36]([CH2:42][C:43]2[C:44]([O:52][C:53](=[O:55])[CH3:54])=[C:45]([CH:49]=[CH:50][CH:51]=2)[C:46]([NH:10][C:9]2[CH:11]=[CH:12][C:6]([S:3]([C:2]([F:13])([F:1])[F:14])(=[O:4])=[O:5])=[CH:7][CH:8]=2)=[O:47])[C:37](=[O:41])[C:38]=1[O:39][CH3:40]
Reactant: Nc1ccc(S(=O)(=O)C(F)(F)F)cc1
Reactant: COC1=C(OC)C(=O)C(Cc2cccc(C(=O)O)c2OC(C)=O)=C(C)C1=O
Agent: CN1CC[NH+](C)C1Cl
Agent: [Cl-]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC1=C(OC)C(=O)C(Cc2cccc(C(=O)Nc3ccc(S(=O)(=O)C(F)(F)F)cc3)c2OC(C)=O)=C(C)C1=O
Temperature: 25 °C
Reaction time: 12 h
Yield: 26.9 %

Procedure:
4-(Trifluoromethylsulfonyl)aniline (0.361 g, 1.604 mmol), triethylamine (0.162 g, 1.604 mmol) and 2-chloro-1,3-dimethylimidazolinium chloride (0.271 g, 1.604 mmol) were added to a methylene chloride solution (50 ml) of 3-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)methyl-2-acetoxybenzoic acid (0.200 g, 0.535 mmol) and the resulting solution was stirred at room temperature for 12 hours. The reaction solution was poured into ice water and then extracted with methylene chloride. The extract was washed with water and then dried, and the solvent was removed by distillation. The obtained residue was purified by preparative thin-layer chromatography (chloroform:methanol=10:1) and then recrystallized from ether to obtain the titled compound (0.084 g, 0.144 mmol, 27%).
Reaction SMILES: [F:1][CH:2]([F:23])[C:3]1[C:7]([C:8]([OH:10])=O)=[C:6]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[N:5]([CH3:22])[N:4]=1.Cl.[NH2:25][C@H:26]([C:28]1[CH:37]=[CH:36][C:31]([C:32]([O:34]C)=[O:33])=[CH:30][CH:29]=1)[CH3:27]>>[CH3:27][C@H:26]([NH:25][C:8]([C:7]1[C:3]([CH:2]([F:23])[F:1])=[N:4][N:5]([CH3:22])[C:6]=1[O:11][C:12]1[CH:13]=[C:14]([C:18]([F:19])([F:21])[F:20])[CH:15]=[CH:16][CH:17]=1)=[O:10])[C:28]1[CH:29]=[CH:30][C:31]([C:32]([OH:34])=[O:33])=[CH:36][CH:37]=1
Reactant: COC(=O)c1ccc([C@H](C)N)cc1
Reactant: Cn1nc(C(F)F)c(C(=O)O)c1Oc1cccc(C(F)(F)F)c1
Agent: Cl
Product: C[C@H](NC(=O)c1c(C(F)F)nn(C)c1Oc1cccc(C(F)(F)F)c1)c1ccc(C(=O)O)cc1

Procedure:
Example 21 was prepared using 3-(difluoromethyl)-1-methyl-5-(3-(trifluoromethyl)phenoxy)-1H-pyrazole-4-carboxylic acid and (S)-methyl 4-(1-aminoethyl)benzoate hydrochloride in a manner similar to the Example 4 above.
Reaction SMILES: CN(C)[CH:3]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]([C:14](=[O:31])[C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:22](=[O:30])[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[Cl:29])=[CH:17][CH:16]=2)[CH2:6][CH2:5][CH2:4]1.CI>C(Cl)(Cl)Cl>[Cl:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[C:22]([NH:21][C:18]1[CH:17]=[CH:16][C:15]([C:14]([N:7]2[C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=3[CH:3]=[CH:4][CH2:5][CH2:6]2)=[O:31])=[CH:20][CH:19]=1)=[O:30]
Reactant: CN(C)C1CCCN(C(=O)c2ccc(NC(=O)c3ccccc3Cl)cc2)c2ccccc21
Solvent: ClC(Cl)Cl
Solvent: CI
Product: O=C(Nc1ccc(C(=O)N2CCC=Cc3ccccc32)cc1)c1ccccc1Cl
Temperature: 100 °C
Reaction time: 3 h
Yield: 57.3 %

Procedure:
A mixture of 5-dimethylamino-1-[4-(2-chlorobenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (10 g), methyl iodide (1.7 ml) and chloroform (10 ml) is heated with stirring at 100° C. for 3 hours in an autoclave. After completion of the reaction, the solvent is distilled off under reduced pressure and the resulting residue is dissolved in methanol. The mixture is treated with IRA-400 (trade mark; Organo Co., Ltd., OH- type). Methanol is distilled off and the resulting residue is suspended in t-butyl alcohol (90 ml), and thereto is added potassium t-butoxide (2.3 g). The mixture is refluxed for 5 hours. The solvent is distilled off under reduced pressure, and the resulting residue is dissolved in dichloromethane. The mixture is washed successively with water and saturated saline solution and dried over magnesium sulfate. The solvent is distilled off and to the resulting residue is added dichloromethane/diethyl ether. The precipitated crude crystal is recrystallized from ethanol to give 1-[4-(2-chlorobenzoylamino)benzoyl]-2,3-dihydro-1H-benzazepine (5.15 g) as colorless needles, m.p. 205°-207° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[O:5][C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-])=O)=[C:8]([CH3:15])[CH:7]=1.[Cl-].[NH4+]>C(O)C.O.[Fe]>[Cl:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[O:5][C:6]1[CH:11]=[CH:10][C:9]([NH2:12])=[C:8]([CH3:15])[CH:7]=1
Reactant: Cc1cc(Oc2cccc(Cl)c2)ccc1[N+](=O)[O-]
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: O
Product: Cc1cc(Oc2cccc(Cl)c2)ccc1N
Yield: 86.8 %

Procedure:
To a stirred solution of 4-(3-chloro-phenoxy)-2-methyl-1-nitro-benzene (0.56 g, 2.12 mmol) in ethanol and water, iron (594 mg, 10.6 mmol) and saturated ammonium chloride (569 mg, 10.6 mmol) were added. This reaction mixture was then heated to reflux for 12 h. This was then filtered through celite and then extracted with EtOAc (3×15 mL). The EtOAc layer was washed with brine, dried over sodium sulfate and concentrated. This was then purified by chromatography (11% EtOAc in hexanes) to afford 4-(3-chloro-phenoxy)-2-methyl-phenylamine (0.43 g, 87%). MS (M+H)+=234.1; 1H NMR (CDCl3) δ: 7.17 (t, J=6.0 Hz, 1H), 6.95 (d, J=2.8 Hz, 1H), 6.88-6.86 (m, 1H), 6.82-6.71 (m, 2H), 6.65 (d, J=6.27 Hz, 1H).
Reaction SMILES: [C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]/[C:4]([OH:6])=[O:5].C([O-])(=O)C.C([O-])(=O)C.[Cu+2:17].C([O-])(=O)C>CO>[Cu:17].[C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]/[C:4]([OH:6])=[O:5]
Reactant: [Cu+2]
Agent: CC(=O)[O-]
Agent: O=C(O)/C=C/C(=O)O
Solvent: CO
Product: [Cu]
Reaction time: 48 h

Procedure:
1.74 g of fumaric acid and 40 cm3 of acetate were dissolved under heating in 100 cm3 of methanol, and into this solution, 100 cm3 of methanol solution containing 2.98 g of copper acetate dissolved therein was dripped. After this solution was left still for two days at the room temperature, the precipitation product was suction-filtered and dried for 110° C./3 hours, whereby 1.37 g of fumaric acid copper was obtained. In this case too, the obtained substance had a large specific surface area and exhibited adsorption capacity for methane.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH2:11][C:12](=[O:18])[NH:13]3)[CH:5]=[CH:6][C:7]=1[F:8].[N:19]1([CH2:24][CH2:25][CH2:26][NH:27][C:28]([C:30]2[CH:34]=[C:33]([CH3:35])[NH:32][C:31]=2[CH:36]=O)=[O:29])[CH2:23][CH2:22][CH2:21][CH2:20]1>C(O)C.N1CCCCC1>[N:19]1([CH2:24][CH2:25][CH2:26][NH:27][C:28]([C:30]2[CH:34]=[C:33]([CH3:35])[NH:32][C:31]=2[CH:36]=[C:11]2[C:10]3[C:14](=[CH:15][CH:16]=[CH:17][C:9]=3[C:4]3[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[CH:3]=3)[NH:13][C:12]2=[O:18])=[O:29])[CH2:23][CH2:22][CH2:21][CH2:20]1
Reactant: Cc1cc(C(=O)NCCCN2CCCC2)c(C=O)[nH]1
Reactant: O=C1Cc2c(cccc2-c2ccc(F)c(Cl)c2)N1
Solvent: C1CCNCC1
Solvent: CCO
Product: Cc1cc(C(=O)NCCCN2CCCC2)c(C=C2C(=O)Nc3cccc(-c4ccc(F)c(Cl)c4)c32)[nH]1
Temperature: 25 °C
Reaction time: 72 h
Yield: 81.3 %

Procedure:
To a solution of 4-(3-chloro-4-fluoro-phenyl)-1,3-dihydro-indol-2-one (65.4 mg, 0.25 mmol) and 2-formyl-5-methyl-1H-pyrrole-3-carboxylic acid (3-pyrrolidin-1-yl-propyl)-amide (68.5 mg, 0.26 mmol) in ethanol (2 mL) was added piperidine (3 drops). The reaction mixture was stirred at room temperature for three days. A yellow solid product was precipitated out, filtered, washed by ethanol for three times, and dried under high vacuum to provide pure product 2-[4-(3-chloro-4-fluoro-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidenemethyl]-5-methyl-1H-pyrrole-3-carboxylic acid (3-pyrrolidin-1-yl-propyl)-amide as a yellow solid (103 mg, 81%).
Reaction SMILES: [H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]([CH:9]=[O:10])[NH:7][CH:8]=1.[C:11]1([CH3:21])[CH:16]=[CH:15][C:14]([S:17](Cl)(=[O:19])=[O:18])=[CH:13][CH:12]=1>C1COCC1>[CH3:21][C:11]1[CH:16]=[CH:15][C:14]([S:17]([N:7]2[C:6]([CH:9]=[O:10])=[CH:5][C:4]([Br:3])=[CH:8]2)(=[O:19])=[O:18])=[CH:13][CH:12]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: O=Cc1cc(Br)c[nH]1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1ccc(S(=O)(=O)n2cc(Br)cc2C=O)cc1
Reaction time: 1 h
Yield: 68.6 %

Procedure:
Following a reported procedure (Tietze, L. F. et al., Synthesis 1996, 851-857), a stirred suspension of NaH (865 mg, 36.0 mmol) in THF (200 mL) was treated with 17 (5.22 g, 30.0 mmol) at room temperature. When the evolution of gas had ceased, the mixture was stirred for 1 h before treating with p-toluenesulfonyl chloride (6.30 g, 33.0 mmol). After 16 h, the conversion was complete as monitored by TLC. The reaction mixture was quenched by adding aqueous NH4Cl. Ethyl acetate was added and the organic layer was separated. The organic layer was washed with water, brine and dried (Na2SO4). Concentration followed by crystallization (ethyl acetate/hexanes) afforded pale yellow crystals (6.75 g, 68%): mp 83-85° C.; 1H NMR δ 2.43 (s, 3H), 7.09 (d, J=2.0 Hz, 1H), 7.35 (d, J=8.3 Hz, 2H), 7.57 (d, J=2.0 Hz, 1H), 7.81 (d, J=8.3 Hz, 2H), 9.94 (s, 1H); 13C NMR δ 22.0, 101.8, 125.4, 127.8, 127.9, 130.6, 133.5, 134.7, 146.7, 178.5. Anal. Calcd or C12H10BrNO3S: C, 43.92; H, 3.07; N, 4.27; S, 9.77. Found: C, 43.92; H, 3.02; N, 4.26; S, 9.84.
Reaction SMILES: [H-].[Na+].[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]([O:14][CH3:15])=[O:13])=[CH:4]1.[CH3:16]I>CN(C=O)C.O>[CH3:16][N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]([O:14][CH3:15])=[O:13])=[CH:4]1
Reactant: CI
Reactant: COC(=O)c1c[nH]c2ccccc12
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1cn(C)c2ccccc12
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 96.3 %

Procedure:
NaH (60% dispersion in mineral oil, 8.56 g, 214.0 mmole) was added portion wise, allowing for gas evolution, to a solution of methyl 1H-indole-3-carboxylate (25.00 g, 142.7 mmole) in DMF (350 mL) at 0° C. When the NaH addition was complete, methyl iodide (44.4 mL, 713.5 mmole) was added at 0° C. The reaction was stirred at 0° C. for 15 minutes then at RT overnight. The reaction was diluted with water and extracted with ethyl acetate. The combined extracts were dried over K2CO3 and concentrated to afford the title compound (26.00 g, 96%) as an orange solid: MS (ES) m/e 190 (M+H)+.