Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.ClC1C=C(C(F)(F)F)C=C(Cl)C=1C1C=C(SC)N(C)N=1.[Cl:32][C:33]1[CH:38]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:36]=[C:35]([Cl:43])[C:34]=1[C:44]1[CH:48]=[C:47]([S:49]([CH3:51])=[O:50])[N:46]([CH3:52])[N:45]=1.S([O-])([O-])=O.[Na+].[Na+]>C(Cl)(Cl)Cl>[Cl:43][C:35]1[CH:36]=[C:37]([C:39]([F:42])([F:40])[F:41])[CH:38]=[C:33]([Cl:32])[C:34]=1[C:44]1[CH:48]=[C:47]([S:49]([CH3:51])(=[O:9])=[O:50])[N:46]([CH3:52])[N:45]=1
Reactant: Cn1nc(-c2c(Cl)cc(C(F)(F)F)cc2Cl)cc1S(C)=O
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: CSc1cc(-c2c(Cl)cc(C(F)(F)F)cc2Cl)nn1C
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: Cn1nc(-c2c(Cl)cc(C(F)(F)F)cc2Cl)cc1S(C)(=O)=O

Procedure:
A 0.3 g quantity of 70% m-chloroperbenzoic acid was slowly added to 0.2 g of 3-(2,6-dichloro-4-trifluoromethylphenyl)-1-methyl-5-methylsulfenylpyrazole (compound 6) in 20 ml of anhydrous chloroform at room temperature with stirring, followed by further stirring overnight. The reaction mixture was poured into a 10% aqueous sodium sulfite solution, an organic layer was then separated off, washed with 5% aqueous sodium hydroxide solution and with brine and dried over anhydrous magnesium sulfate. The solvent was thereafter distilled off under reduced pressure, giving 0.3 g of the desired compound in the form of white crystals (quantitative crude yield).
Reaction SMILES: N[C:2]1[CH:3]=[C:4]2[CH2:16][CH2:15][C:14]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[CH:8]([CH:17]3[CH2:22][CH2:21][N:20]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:19][CH2:18]3)[C:5]2=[N:6][CH:7]=1.[Br:28]Br.N([O-])=O.[Na+].[OH-].[Na+]>Br.O>[Br:28][C:2]1[CH:3]=[C:4]2[CH2:16][CH2:15][C:14]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[CH:8]([CH:17]3[CH2:22][CH2:21][N:20]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:19][CH2:18]3)[C:5]2=[N:6][CH:7]=1
Reactant: CCOC(=O)N1CCC(C2c3ncccc3CCc3cc(N)cnc32)CC1
Reactant: BrBr
Agent: Br
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Product: CCOC(=O)N1CCC(C2c3ncccc3CCc3cc(Br)cnc32)CC1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 59.8 %

Procedure:
Ethyl 4-(3-amino-6,11-dihydro-5H-cyclohepta[2,1-b:4,5-b′]dipyridin-11-yl)-1-piperidinecarboxylate ( 0.05 gm, 0.136 mmol) was dissolved in 4 ml of 48% hydrobromic acid. The reaction mixture was cooled to 0° C. and bromine (0.038 ml, 0.738 mmol) was added dropwise and stirred for 15 minutes. Sodium nitrite (0.028 gm, 0.408 mmol) was added, as a solution in 0.5 ml of water, dropwise over 15 minutes. The reaction was stirred at 0° C. for 3-4 hours. The reaction mixture was basified to pH 10 with 10% sodium hydroxide and the produt extracted into ethylacetate. The ethylacetate layer was dried over magnesium sulfate, filtered and evaporated to dryness. The crude product was chromatographed on silica gel using 10-20% methanol/dichoromethane as the eluent to obtain 0.035 gm of title product. FABMS (M+1)=431
Reaction SMILES: [F:1][C:2]1[C:3]([N:17]=[CH:18][N:19]([CH3:21])[CH3:20])=[N:4][C:5](=[O:16])[N:6](CC2C=CC(C)=CC=2)[CH:7]=1>CCO.[Cl-].[Zn+2].[Cl-]>[F:1][C:2]1[C:3]([N:17]=[CH:18][N:19]([CH3:21])[CH3:20])=[N:4][C:5]([OH:16])=[N:6][CH:7]=1
Reactant: Cc1ccc(Cn2cc(F)c(N=CN(C)C)nc2=O)cc1
Agent: [Cl-]
Agent: [Zn+2]
Solvent: CCO
Product: CN(C)C=Nc1nc(O)ncc1F
Temperature: 25 °C
Reaction time: 2 h
Yield: 99.3 %

Procedure:
Zinc chloride (1.24 g, 9.12 mmol) was added to a mixture of the formamidine product from Step 2 (0.656 g, 2.28 mmol) in absolute EtOH (10 mL). The resultant mixture was heated to reflux under N2. The mixture gradually turned into a light yellow, homogeneous solution. After refluxing for 90 min a precipitate had formed, and after 2 h, the reaction mixture was allowed to cool to room temperature and was concentrated in vacuo. The residue was treated with CH2Cl2 (75 mL, slightly turbid in appearance) and washed with H2O (25 mL). As soon as H2O was added a white precipitate formed in both layers in the separatory funnel. The solid was removed by vacuum filtration. The solid was washed with H2O followed by Et2O. After air-drying overnight the white solid (0.58 g) was treated with 1:1 CH2Cl2/MeOH (˜70 mL) and heated to reflux (turbid mixture). The mixture was filtered and the filtrate was concentrated in vacuo. The residual solid was slurried with hexanes/Et2O (˜3:1) and isolated by vacuum filtration, air-dried and then vacuum oven dried (70-80° C.) to give N′-(5-fluoro-2-hydroxypyrimidin-4-yl)-N,N-dimethylformamidine (0.417 g, 78%) as a white powder: mp 291-293° C. dec; 1H NMR (300 MHz, DMSO-d6) δ 8.03 (d, J=6.9 Hz, 1H), 7.62 (br s, 1H), 7.40 (br s, 1H), 7.17 (d, J=7.8 Hz, 2H), 7.12 (d, J=8.1 Hz, 2H), 4.73 (s, 2H), 2.25 (s, 3H); 13C NMR (150 MHz, DMSO-d6) δ 158.2, 154.8, 137.3, 136.3 (d, J=240 Hz), 135.3, 131.1 (d, J=30.6 Hz), 129.7, 128.3, 51.8, 21.3; ESIMS m/z 234 ([M+H]+), m/z 232 ([M−H]−); IR 3298 (m, br), 3100 (m, br), 1685 (s), 1619 (s), 1518 (s), 1447 (m), 1383 (m), 1343 (w), 1120 (w), 776 (w) cm−1.
Reaction SMILES: [C:1]([OH:12])(=[O:11])[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.C([O-])(=O)C.[Mo+4:17].C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C>CO>[Mo:17].[C:1]([OH:12])(=[O:11])[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1
Reactant: [Mo+4]
Agent: CC(=O)[O-]
Agent: O=C(O)c1ccc(C(=O)O)cc1
Solvent: CO
Product: [Mo]
Temperature: 25 °C
Reaction time: 72 h

Procedure:
0.854 g (5.14 mmol) of terephthalic acid and 1,000 g (2.34 mmol) of molybdenum acetate were dissolved in 900 ml of methanol. After this was stirred for three days at the room temperature, this was kept still for a few days. Thereafter, its precipitation product was suction-filtered, rinsed sufficiently with methanol and then vacuum-dried for 60° C./4 hours, whereby 1.387 g of target substance was obtained. This substance had the specific surface area of 519 m2 /g. And, a measurement according to the HK method using argon revealed that the substance had the pore diameter of 5.7 Å.
Reaction SMILES: [CH2:1]([C:3]1[C:4]([C:12]([O:14]C)=O)=[C:5]([N:9]=[C:10]=[S:11])[S:6][C:7]=1[CH3:8])C.[CH3:16][C:17]1[N:18]=[CH:19][N:20]([CH2:22][CH2:23][CH2:24][NH2:25])[CH:21]=1>>[CH3:1][C:3]1[C:4]2[C:12](=[O:14])[N:25]([CH2:24][CH2:23][CH2:22][N:20]3[CH:21]=[C:17]([CH3:16])[N:18]=[CH:19]3)[C:10](=[S:11])[NH:9][C:5]=2[S:6][C:7]=1[CH3:8]
Reactant: Cc1cn(CCCN)cn1
Reactant: CCc1c(C)sc(N=C=S)c1C(=O)OC
Product: Cc1cn(CCCn2c(=S)[nH]c3sc(C)c(C)c3c2=O)cn1

Procedure:
The compound was synthesized starting from methyl 4-ethyl-2-isothiocyanato-5-methylthiophene-3-carboxylate (0.110 g. 0.46 mmol) and 3-(4-methyl-1H-imidazol-1-yl)propan-1-amine (9) (0.063 g, 0.46 mmol) as described above.
Reaction SMILES: [F:1][C:2]([F:19])([F:18])[C:3]1[CH:4]=[C:5]([CH:15]=[CH:16][CH:17]=1)[NH:6][CH:7]=[C:8]([C:12]([O-:14])=O)[C:9]([O-:11])=[O:10].[CH:20]1C=CC(C2C=CC=CC=2)=C[CH:21]=1.C1C=CC(OC2C=CC=CC=2)=CC=1>>[OH:14][C:12]1[C:15]2[C:5](=[CH:4][C:3]([C:2]([F:1])([F:19])[F:18])=[CH:17][CH:16]=2)[N:6]=[CH:7][C:8]=1[C:9]([O:11][CH2:20][CH3:21])=[O:10]
Reactant: c1ccc(-c2ccccc2)cc1
Reactant: O=C([O-])C(=CNc1cccc(C(F)(F)F)c1)C(=O)[O-]
Solvent: c1ccc(Oc2ccccc2)cc1
Product: CCOC(=O)c1cnc2cc(C(F)(F)F)ccc2c1O
Temperature: 240 °C
Reaction time: 3 h

Procedure:
Under a nitrogen atmosphere, a mixture of 2-{[3-(trifluoromethyl)anilino]methylene}malonate (80 g, 0.24 mol) and Dowtherm A was heated to 240° C. and then stirred for 3 hours. The reaction mixture was allowed to cool to ambient temperature and then stirred for 16 hours. The solids were isolated by filtration then washed with hexane to provide 47.5 g of ethyl 4-hydroxy-7-(trifluoromethyl)-3-quinolinecarboxylate as an off-white solid.
Reaction SMILES: [CH2:1]([N:3]([CH2:13][CH3:14])[C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=1)[CH3:2].[CH3:15][CH2:16][CH2:17][CH:18]([NH2:22])[CH2:19][CH2:20][CH3:21]>>[CH2:13]([N:3]([CH2:1][CH3:2])[C:4]1[CH:5]=[CH:6][C:7]([C:8]([NH:22][CH:18]([CH2:19][CH2:20][CH3:21])[CH2:17][CH2:16][CH3:15])=[O:10])=[CH:11][CH:12]=1)[CH3:14]
Reactant: CCN(CC)c1ccc(C(=O)O)cc1
Reactant: CCCC(N)CCC
Product: CCCC(CCC)NC(=O)c1ccc(N(CC)CC)cc1

Procedure:
Prepared in a similar manner to example 4 using 4-diethylamino benzoic acid and 4-heptylamine. (31% %). NMR (500 MHz, CDCl3): δ 0.92 (t, 6H, J=7.17 Hz), 1.18 (t, 6H, J=7.04 Hz), 1.41 (m, 4H), 1.55 (m, 4H), 3.39 (m, 4H), 4.15 (m, 1H), 5.62 (m, 1H), 6.64 (d, 2H, J=10.26 Hz), 7.64 (d, 2H, J=10.26 Hz). MS (M+H, 291).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[NH:11][C:10]([CH2:12][CH2:13][CH2:14][CH3:15])=[N:9][C:5]2=[N:6][C:7]=1[CH3:8].ClC1C=CC=C(C(OO)=[O:24])C=1>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[NH:11][C:10]([CH2:12][CH2:13][CH2:14][CH3:15])=[N:9][C:5]2=[N+:6]([O-:24])[C:7]=1[CH3:8]
Reactant: CCCCc1nc2nc(C)c(Br)cc2[nH]1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CCCCc1nc2c(cc(Br)c(C)[n+]2[O-])[nH]1
Temperature: 25 °C
Reaction time: 16 h
Yield: 96.7 %

Procedure:
7.8 g (29.1 mmole) of the compound obtained in step 4 was dissolved in 50 ml of methylene chloride and to the resulting solution was added 8.8 g (43.6 mmole) of 85% m-chloroperbenzoic acid. The resultant was stirred for 16 hours at room temperature and filtered to get a solid, which was washed with ethyl ether (12 ml×3) to obtain 8.0 g of the title compound (yield 97%).
Reaction SMILES: [Cl:1][C:2]1[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:3]=1[C:4]([C:6]1[S:10][C:9]2[C:11]([C:15]([O:17]C)=[O:16])=[CH:12][CH:13]=[CH:14][C:8]=2[C:7]=1[CH2:19][CH3:20])=O.O.NN.[OH-].[K+].Cl>C(O)CO>[C:15]([C:11]1[C:9]2[S:10][C:6]([CH2:4][C:3]3[CH:21]=[CH:22][C:23]([Cl:25])=[CH:24][C:2]=3[Cl:1])=[C:7]([CH2:19][CH3:20])[C:8]=2[CH:14]=[CH:13][CH:12]=1)([OH:17])=[O:16]
Reactant: CCc1c(C(=O)c2ccc(Cl)cc2Cl)sc2c(C(=O)OC)cccc12
Agent: Cl
Agent: NN
Agent: [K+]
Solvent: OCCO
Solvent: O
Product: CCc1c(Cc2ccc(Cl)cc2Cl)sc2c(C(=O)O)cccc12
Temperature: 160 °C
Reaction time: 2 h
Yield: 74.8 %

Procedure:
2-(2,4-Dichlorobenzoyl)-3-ethyl-7-(methoxycarbonyl)benzo[b]thiophene (2.85 g) and hydrazine hydrate (3.50 g) were stirred in ethylene glycol (30 ml) at 160° C. for 1 hr. After cooling, potassium hydroxide (3.30 g) was added, and the mixture was stirred at 160° C. for 2 hr. After cooling, ice and concentrated hydrochloric acid were added, and the mixture was extracted with ethyl acetate. The extract was dried over sodium sulfate and concentrated, and the residue was purified by silica gel column chromatography to give the objective compound (1.98 g) as white crystals.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([F:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[C:13](Cl)(=O)C>CO>[CH3:13][O:5][C:4](=[O:6])[C:3]1[CH:7]=[C:8]([F:12])[C:9]([F:11])=[CH:10][C:2]=1[Cl:1]
Reactant: CC(=O)Cl
Reactant: O=C(O)c1cc(F)c(F)cc1Cl
Solvent: CO
Product: COC(=O)c1cc(F)c(F)cc1Cl
Yield: 84 %

Procedure:
To a stirred suspension of 5.0 g (26 mmol) 2-Chloro-4,5-difluoro-benzoic acid (Apollo) and 50 ml methanol were added 7.41 ml (104 mmol) acetyl chloride drop wisely at 0° C. The reaction mixture was stirred over night, filtered and concentrated. The residue was diluted with dichloromethane, washed with diluted sodium hydrogen carbonate solution, dried with sodium sulphate and concentrated. The residue was purified by column chromatography (hexane:ethylacetate). The desired product 22a was obtained in 84% yield (4.51 g, 21.8 mmol).
Reaction SMILES: [CH2:1]([N:3](CC)CC)[CH3:2].Cl.C(=N)(OCC)C.[NH:15]1[CH2:20][CH2:19][CH:18]([CH2:21][O:22][C:23]2[CH:24]=[C:25]([O:30][S:31]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[Cl:40])(=[O:33])=[O:32])[CH:26]=[C:27]([CH3:29])[CH:28]=2)[CH2:17][CH2:16]1>CN(C)C=O>[ClH:40].[C:1]([N:15]1[CH2:20][CH2:19][CH:18]([CH2:21][O:22][C:23]2[CH:24]=[C:25]([O:30][S:31]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[Cl:40])(=[O:32])=[O:33])[CH:26]=[C:27]([CH3:29])[CH:28]=2)[CH2:17][CH2:16]1)(=[NH:3])[CH3:2]
Reactant: CCN(CC)CC
Reactant: Cc1cc(OCC2CCNCC2)cc(OS(=O)(=O)c2ccccc2Cl)c1
Agent: CCOC(C)=N
Agent: Cl
Solvent: CN(C)C=O
Product: CC(=N)N1CCC(COc2cc(C)cc(OS(=O)(=O)c3ccccc3Cl)c2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 86 %

Procedure:
Triethylamine (0.5 mL) and ethyl acetimidate hydrochloride (247 mg, 2.0 mmol) were added to a solution of 2-chlorobenzenesulfonic acid 3-[(piperidin-4-yl)methoxy]-5-methylphenyl ester (396 mg, 1.0 mmol), as prepared in the preceding step, in N,N-dimethylformamide (10 mL). The reaction mixture was stirred at room temperature overnight. The N,N-dimethylformamide was removed in vacuo and the residue partitioned between methylene chloride (200 mL) and 10% K2CO3 (50 mL). The organic phase was washed with 10% K2CO3 (2×50 mL) and dried over K2CO3. The solvent was removed in vacuo, HCl-methanol (30 mL) was added, and the solution was concentrated in vacuo. The residue was crystallized from methanol-ethyl acetate to give the title compound as white crystals (405 mg, 86%). 1H-NMR (300 MHz, DMSO-d6) δ 1.30 (m, 2H), 1.82 (d, 2H, J=7.0 Hz), 2.05 (m, 1H), 2.20 (s, 3H), 2.29 (s, 3H), 3.16 (m, 2H), 3.77 (d, 2H, J=3.0 Hz), 3.92 (d, 1H, J=6.5 Hz), 4.17 (d, 1 H J=6.5 Hz), 6.46 (d, 1H, J=2.5 Hz), 6.49 (s, 1H), 7.59 (t, 1 H. J=8.0 Hz), 7.87 (m, 2H), 7.95 (d, 1H, J=8.0 Hz), 8.77 (br s, 1H), and 9.35 (br s, 1H). Mass spectrum MALDI-TOF, sinapinic acid matrix) calcd. for C21H25N2O4SCl: 437.1 (M+H). Found: 436.8.
Reaction SMILES: N#N.C([Si](C)(C)[O:8][CH:9]([C:11]1[O:12][C:13]([CH2:16][N:17]2[N:21]=[C:20]([NH:22][C:23]([C:25]3[N:26]=[C:27]([CH3:37])[O:28][C:29]=3[C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[CH:31]=3)=[O:24])[CH:19]=[N:18]2)=[CH:14][N:15]=1)[CH3:10])(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.CC(=O)OCC>[OH:8][CH:9]([C:11]1[O:12][C:13]([CH2:16][N:17]2[N:21]=[C:20]([NH:22][C:23]([C:25]3[N:26]=[C:27]([CH3:37])[O:28][C:29]=3[C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[CH:31]=3)=[O:24])[CH:19]=[N:18]2)=[CH:14][N:15]=1)[CH3:10]
Reactant: Cc1nc(C(=O)Nc2cnn(Cc3cnc(C(C)O[Si](C)(C)C(C)(C)C)o3)n2)c(-c2cccc(Cl)c2)o1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: N#N
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Cc1nc(C(=O)Nc2cnn(Cc3cnc(C(C)O)o3)n2)c(-c2cccc(Cl)c2)o1
Temperature: 0 °C
Reaction time: 0.75 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 5-(3-chloro-phenyl)-2-methyl-oxazole-4-carboxylic acid (2-{2-[1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-oxazol-5-ylmethyl}-2H-[1,2,3]triazol-4-yl)-amide (106 mg, 0.20 mmol) in dry THF (1.9 mL) was treated at 0° C. with TBAF (0.39 mL of a 1M solution in THF, 0.39 mmol). The reaction mixture was stirred at 0° C. for 45 min. The mixture was then diluted with EA (10 mL), washed with NaHCO3 (10 mL) followed by brine (3×10 mL), dried over MgSO4, filtered and concentrated under reduced pressure. Purification of the residue by FC (19:1 CH2Cl2-MeOH) gave the title compound as a white solide. TLC:rf (19:1 CH2Cl2-MeOH)=0.22. LC-MS-conditions 01: tR=0.93 min; [M+H]+=428.97.
Reaction SMILES: [CH2:1]([N:4]([CH2:8][CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][NH:10]1)[CH2:5][CH2:6]C)[CH2:2]C.BrCC#N.C([N:22]([CH2:26][CH:27]1[CH2:32][CH2:31]CCN1CC#N)CCC)CC>ClCCl.C(OCC)(=O)C>[CH2:1]([N:4]([CH2:8][CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][N:10]1[CH2:31][CH2:32][CH2:27][C:26]#[N:22])[CH2:5][CH3:6])[CH3:2]
Reactant: CCCN(CCC)CC1CCCCN1
Reactant: CCCN(CCC)CC1CCCCN1CC#N
Agent: N#CCBr
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CCN(CC)CC1CCCCN1CCCC#N

Procedure:
from 2-[(dipropylamino)methyl]piperidine and 2-bromoacetonitrile, (±)-2-[2-[(dipropylamino)methyl]piperidin-1-yl]acetonitrile, RF 0.9 (Macherey-Nagel, PolygramRSIL G/UV254, pre-coated plastic sheets for TLC, eluant: dichloromethane/ethyl acetate 50:50 v/v).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:11]=[C:12]([CH2:21]OS(C)(=O)=O)[C:13](=[O:20])[N:14]([CH2:16][CH:17]([CH3:19])[CH3:18])[N:15]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[CH3:27][N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1>>[F:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:11]=[C:12]([CH2:21][N:31]3[CH2:32][CH2:33][N:28]([CH3:27])[CH2:29][CH2:30]3)[C:13](=[O:20])[N:14]([CH2:16][CH:17]([CH3:18])[CH3:19])[N:15]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9]
Reactant: CN1CCNCC1
Reactant: COc1ccc(-c2cc(COS(C)(=O)=O)c(=O)n(CC(C)C)n2)cc1F
Product: COc1ccc(-c2cc(CN3CCN(C)CC3)c(=O)n(CC(C)C)n2)cc1F
Yield: 80.9 %

Procedure:
Following the procedure of Example 1(10), 6-(3-fluoro-4-methoxyphenyl)-2-isobutyl-4-methanesulfonyloxymethyl-2H-pyridazin-3-one and 1-methylpiperazine were reacted to yield the title compound as a yellow oil (yield: 80.9%).
Reaction SMILES: [CH2:1]([S:3]([N:6]1[CH2:11][CH2:10][CH:9]([C:12]2[C:20]3[C:15](=[C:16]([C:29]([NH2:31])=[O:30])[CH:17]=[C:18]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([CH:27]=O)[CH:22]=4)[CH:19]=3)[NH:14][CH:13]=2)[CH2:8][CH2:7]1)(=[O:5])=[O:4])[CH3:2].[CH:32]1([NH2:37])[CH2:36][CH2:35][CH2:34][CH2:33]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[CH:32]1([NH:37][CH2:27][C:23]2[CH:22]=[C:21]([C:18]3[CH:19]=[C:20]4[C:15](=[C:16]([C:29]([NH2:31])=[O:30])[CH:17]=3)[NH:14][CH:13]=[C:12]4[CH:9]3[CH2:8][CH2:7][N:6]([S:3]([CH2:1][CH3:2])(=[O:4])=[O:5])[CH2:11][CH2:10]3)[CH:26]=[CH:25][CH:24]=2)[CH2:36][CH2:35][CH2:34][CH2:33]1
Reactant: NC1CCCC1
Reactant: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4cccc(C=O)c4)cc23)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Product: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4cccc(CNC5CCCC5)c4)cc23)CC1
Yield: 72.1 %

Procedure:
Following the general procedure of example 5, 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-(3-formylphenyl)-1H-indole-7-carboxamide (45 mg, 0.101 mmol), cyclopentylamine (90 uL, 0.090 mmol) and NaBH(OAc)3 (197 mg, 0.93 mmol) were reacted to give the title compound (33.0 mg, 64%).
Reaction SMILES: [Mg].C(O[CH2:5][CH3:6])C.[CH3:7][C:8]12[CH2:18][CH:12]3[CH2:13][C:14]([CH3:17])([CH2:16][C:10](Br)([CH2:11]3)[CH2:9]1)[CH2:15]2>ClCCl.O>[CH3:7][C:8]12[CH2:18][CH:12]3[CH2:13][C:14]([CH3:17])([CH2:16][C:10]([C:14]45[CH2:15][C:8]6([CH3:18])[CH2:9][CH:10]([CH2:11][C:5]([CH3:6])([CH2:7]6)[CH2:13]4)[CH2:16]5)([CH2:11]3)[CH2:9]1)[CH2:15]2
Reactant: CCOCC
Reactant: CC12CC3CC(C)(C1)CC(Br)(C3)C2
Agent: [Mg]
Solvent: O
Solvent: ClCCl
Product: CC12CC3CC(C)(C1)CC(C14CC5CC(C)(CC(C)(C5)C1)C4)(C3)C2
Yield: 47 %

Procedure:
Into a 2 liter egg plant-shaped flask, 9.8 g (0.4 moles) of magnesium was weighed and placed. Under the stream of nitrogen gas, 80 ml of diethyl ether was added and stirred. Then, a solution prepared by dissolving 97.28 g (0.4 moles) of 3,5-dimethyl-1-bromoadamantane into 40 ml of diethyl ether was added dropwise. After the addition was completed, the resultant mixture was heated under the refluxing condition for 30 minutes. The temperature was adjusted at the room temperature, and diethyl ether was completely removed using a vacuum pump. Then, a solution prepared by dissolving 48.64 g (0.2 moles) of 3,5-dimethyl-1-bromoadamantane into 600 ml of dichloromethane was added dropwise. After the addition was completed, the resultant mixture was heated under the refluxing condition for 5 hours. The reaction fluid was poured into 400 ml of ion-exchanged water and treated by extraction with dichloromethane using a separation funnel. The solvent was removed using an evaporator. The residue was dissolved into 40 ml of hexane and purified in accordance with the silica gel column chromatography (the solvent of development: hexane). The solvent was removed using an evaporator, and 30.70 g of 3,3′,5,5′-tetramethyl-1,1′-biadamantane was obtained (the yield: 47%). Since the molecular weight was 327 in the mass analysis, it was shown that the product was the object compound.
Reaction SMILES: B([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[C:7]([OH:9])=[O:8])(O)O.Br[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[N:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[C:7]([OH:9])=[O:8]
Reactant: O=C(O)c1cccc(B(O)O)c1
Reactant: Brc1ccccn1
Agent: Cl[Pd]Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Product: O=C(O)c1cccc(-c2ccccn2)c1
Temperature: 100 °C
Reaction time: 24 h
Yield: 84.8 %

Procedure:
To a solution of 3-boronobenzoic acid (1.66 g, 10 mmol) and 2-bromopyridine (1.72 g, 11 mmol) in acetonitrile (40 mL) and water (40 mL), potassium carbonate (5.5 g, 40 mmol), Bis(triphenylphosphine)palladium(II)chloride (400 mg, 0.37 mmol) was added. The mixture was degassed and purged withed nitrogen. The mixture was stirred at 100° C. for 24 h. Then the hot suspension was filtered and concentrated to half of the original volume and washed with dichloromethane. The aquatic phase was adjusted to pH=3 with hydrochloric acid (1 M) and filtrated, washed with water. The residue was dried in vacuum to obtain 1.69 g of white solid of 3-(pyridin-2-yl)benzoic acid. Yield: 85%. LC-MS (ESI) m/z: 200 (M+1)+.
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5]1[CH:19]=[CH:18][C:8]([CH2:9][NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:7][CH:6]=1.[CH:20]([P:23](=[O:29])([CH:26]([CH3:28])[CH3:27])[CH:24]=[CH2:25])([CH3:22])[CH3:21]>C1COCC1>[CH:20]([P:23]([CH2:24][CH2:25][N:10]([CH2:9][C:8]1[CH:18]=[CH:19][C:5]([O:4][CH3:3])=[CH:6][CH:7]=1)[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:14])[CH3:15])([CH:26]([CH3:28])[CH3:27])=[O:29])([CH3:22])[CH3:21]
Reactant: C=CP(=O)(C(C)C)C(C)C
Reactant: COc1ccc(CNC(=O)OC(C)(C)C)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1ccc(CN(CCP(=O)(C(C)C)C(C)C)C(=O)OC(C)(C)C)cc1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a suspension of NaH (60%, 157 mg, 3.93 mmol) in THF (5 mL) at 0° C. was added tert-butyl (4-methoxybenzyl)carbamate (889 mg, 3.75 mmol) in THF (5 mL). After stirring for 30 minutes at 0° C., diisopropyl(vinyl)phosphine oxide (300 mg, 1.873 mmol) in THF (3 mL) was added. The reaction was allowed to slowly warn to room temperature and subsequently heated to 60° C. for 3 h. The mixture was quenched with saturated NH4Cl and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (MgSO4), and evaporated. Flash chromatography (0-10% MeOH/EtOAc) afforded the title compound as a pale yellow oil. MS: cal'd 398 (MH+), exp 398 (MH+).
Reaction SMILES: [CH3:1][C:2]1[CH:41]=[C:40]([CH3:42])[CH:39]=[CH:38][C:3]=1[O:4][CH2:5][C@H:6]([OH:37])[CH2:7][NH:8][C:9]1[CH:14]=[CH:13][NH:12][C:11](=[O:15])[C:10]=1[C:16]1[NH:17][C:18]2[C:26]([N:27]=1)=[CH:25][C:24]1[C:23](=O)[N:22]([CH:29]3[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]3)[C:21](=[O:36])[C:20]=1[CH:19]=2>CC(O)=O.[Zn]>[CH3:1][C:2]1[CH:41]=[C:40]([CH3:42])[CH:39]=[CH:38][C:3]=1[O:4][CH2:5][C@H:6]([OH:37])[CH2:7][NH:8][C:9]1[CH:14]=[CH:13][NH:12][C:11](=[O:15])[C:10]=1[C:16]1[NH:17][C:18]2[C:26](=[CH:25][C:24]3[CH2:23][N:22]([CH:29]4[CH2:30][CH2:31][N:32]([CH3:35])[CH2:33][CH2:34]4)[C:21](=[O:36])[C:20]=3[CH:19]=2)[N:27]=1
Reactant: Cc1ccc(OC[C@H](O)CNc2cc[nH]c(=O)c2-c2nc3cc4c(cc3[nH]2)C(=O)N(C2CCN(C)CC2)C4=O)c(C)c1
Agent: [Zn]
Solvent: CC(=O)O
Product: Cc1ccc(OC[C@H](O)CNc2cc[nH]c(=O)c2-c2nc3cc4c(cc3[nH]2)C(=O)N(C2CCN(C)CC2)C4)c(C)c1
Temperature: 90 °C
Yield: 83.7 %

Procedure:
2-{4-[(R)-3-(2,4-Dimethyl-phenoxy)-2-hydroxy-propylamino]-2-oxo-1,2-dihydro-pyridin-3-yl}-6-(1-methyl-piperidin-4-yl)-1H-1,3,6-triaza-s-indacene-5,7-dione (3.0 g, 5.26 mmol) was mixed with zinc dust (6.88 g, 10.52 mmol) in AcOH (150 mL). After it was heated at 90° C. for 2 h, the reaction mixture was filtered and the filtrate was evaporated at 95° C. (the bath temperature) under reduced pressure to dryness. The residue was basified with 28% aqueous NH4OH solution and concentrated. Chromatography of the residual crude with CH2Cl2/MeOH/28% aqueous NH4OH (90:10:1) afforded the title compound (2.45 g, 84%). 1H NMR (DMSO-d6) δ 1.70 (m, 2H), 1.80 (m, 2H), 2.05 (m, 2H), 2.20 (s, 3H, CH3), 2.22 (s, 3H, CH3), 2.28 (s, 3H, CH3), 2.89 (m, 2H), 3.57 (m, 1H), 3.79 (m, 1H), 3.95-4.09 (3H), 4.11 (m, 1H), 4.40 (s, 1H), 4.45 (s, 1H), 5.47 (d, J=3 Hz, 0.5H, NH), 5.54 (d, J=3 Hz, 0.5H, NH), 6.21 (m, 1H), 6.80-7.00 (3H), 7.30-7.39 (1.5H), 7.69 (s, 0.5H), 7.79 (s, 0.5H), 7.93 (s, 0.5H), 11.12 (br d, J=6 Hz, 1H, NH), 11.22 (br d, J=6 Hz, 1H, NH); ESI-MS m/z 557.7 (MH+).