Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH2:14][CH2:15][CH2:16][N:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)[C:9](=[O:23])[CH2:8][CH2:7]2)([O-])=O.O.NN>CO.[Ni]>[NH2:1][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH2:14][CH2:15][CH2:16][N:17]1[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]1)[C:9](=[O:23])[CH2:8][CH2:7]2
Reactant: O=C1CCc2cc([N+](=O)[O-])ccc2N1CCCN1CCCCC1
Agent: [Ni]
Agent: NN
Solvent: O
Solvent: CO
Product: Nc1ccc2c(c1)CCC(=O)N2CCCN1CCCCC1
Temperature: 25 °C

Procedure:
6-nitro-1-(3-(piperidin-1-yl)propyl)-3,4-dihydroquinolin-2(1H)-one (98 mg, 0.309 mmol) in dry methanol (5 mL) was treated with Ra—Ni (˜0.05 g slurry in water) followed by hydrazine hydrate (96 uL, 3.08 mmol) at room temperature and the resulting mixture was refluxed for 30 minutes. The reaction was cooled to room temperature, filtered through a celite bed, washed with methanol (2×10 mL). The combined methanol layer was evaporated and crude was purified by column chromatography (2 M NH3 in MeOH:CH2Cl2, 2.5:97.5). Yield: 71 mg of yellow oil (80%). 1H NMR (CDCl3) δ: 6.90 (d, J=8.4 Hz, 1H), 6.55 (dd, J=2.7, 8.4 Hz, 1H), 6.51 (d, J=2.1 Hz, 1H), 3.91 (m, 2H), 2.80-2.76 (m, 2H), 2.61-2.56 (m, 2H), 2.38-2.33 (m, 6H), 1.84-1.79 (m, 2H), 1.60-1.55 (m, 4H), 1.46-1.42 (m, 2H). MS (ESI): 288.2 (M+1).
Reaction SMILES: I[C:2]1[C:11](=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[N:15]=2)[CH:3]=1.C([Mg]Cl)(C)C.[Cl:26][C:27]1[CH:38]=[CH:37][C:30]([C:31](N(OC)C)=[O:32])=[CH:29][CH:28]=1>C1COCC1>[Cl:26][C:27]1[CH:38]=[CH:37][C:30]([C:31]([C:2]2[C:11](=[O:12])[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[N:4]([CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[N:15]=3)[CH:3]=2)=[O:32])=[CH:29][CH:28]=1
Reactant: Cc1cccc(Cn2cc(I)c(=O)c3ccccc32)n1
Reactant: CON(C)C(=O)c1ccc(Cl)cc1
Agent: CC(C)[Mg]Cl
Solvent: C1CCOC1
Product: Cc1cccc(Cn2cc(C(=O)c3ccc(Cl)cc3)c(=O)c3ccccc32)n1
Reaction time: 2 h

Procedure:
A −78° C. solution of 3-iodo-1-(6-methyl-pyridin-2-ylmethyl)-1H-quinolin-4-one (113 mg, 0.3 mmol, 1 equiv) in 3 mL of THF was treated with 1.65 mL of isopropyl magnesium chloride (1.1 equiv) for 2 hours. Then 4-chloro-N-methoxy-N-methyl-benzamide (46 μL, 1.2 equiv) was added and stirring continued at rt for 2 hours. The reaction was quenched by slow addition of saturated aqueous solution of NH4Cl. Standard workup followed by HPLC purification gave 3-(4-chloro-benzoyl)-1-(6-methyl-pyridin-2-ylmethyl)-1H-quinolin-4-one. LCMS (ES) M+H 389.1
Reaction SMILES: [O:1]=[C:2]1[N:8]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C@@H:18]([C:31]([OH:33])=O)[CH2:19][C:20]3[CH:29]=[C:28]([CH3:30])[C:23]4[NH:24][C:25](=[O:27])[O:26][C:22]=4[CH:21]=3)=[O:16])[CH2:11][CH2:10]2)[CH2:7][CH2:6][C:5]2[CH:34]=[CH:35][CH:36]=[CH:37][C:4]=2[NH:3]1.[NH:38]1[CH2:43][CH2:42][CH:41]([N:44]2[CH2:49][CH2:48][N:47]([C:50](=[O:52])[CH3:51])[CH2:46][CH2:45]2)[CH2:40][CH2:39]1>>[O:1]=[C:2]1[N:8]([CH:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][C@H:18]([CH2:19][C:20]3[CH:29]=[C:28]([CH3:30])[C:23]4[NH:24][C:25](=[O:27])[O:26][C:22]=4[CH:21]=3)[C:31]([N:38]3[CH2:39][CH2:40][CH:41]([N:44]4[CH2:45][CH2:46][N:47]([C:50](=[O:52])[CH3:51])[CH2:48][CH2:49]4)[CH2:42][CH2:43]3)=[O:33])=[O:16])[CH2:13][CH2:14]2)[CH2:7][CH2:6][C:5]2[CH:34]=[CH:35][CH:36]=[CH:37][C:4]=2[NH:3]1
Reactant: CC(=O)N1CCN(C2CCNCC2)CC1
Reactant: Cc1cc(C[C@@H](OC(=O)N2CCC(N3CCc4ccccc4NC3=O)CC2)C(=O)O)cc2oc(=O)[nH]c12
Product: CC(=O)N1CCN(C2CCN(C(=O)[C@@H](Cc3cc(C)c4[nH]c(=O)oc4c3)OC(=O)N3CCC(N4CCc5ccccc5NC4=O)CC3)CC2)CC1

Procedure:
Prepared analogously to Example 1 h from 600 mg (1.18 mmol) (R)-1-carboxy-2-(4-methyl-2-oxo-2,3-dihydrobenzoxazol-6-yl)-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate and 275 mg (1.30 mmol) 1-(4-piperidin-4-yl-piperazin-1-yl)-ethanone.
Reaction SMILES: [OH:1][N:2]1[C:6](=[O:7])[C:5]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:4]2[C:3]1=[O:12].[CH2:13]1[CH2:23]CN2C(=NCCC2)C[CH2:14]1.C(Br)C=C>CN(C=O)C>[CH2:23]([O:1][N:2]1[C:3](=[O:12])[C:4]2=[CH:11][CH:10]=[CH:9][CH:8]=[C:5]2[C:6]1=[O:7])[CH:13]=[CH2:14]
Reactant: C1CCC2=NCCCN2CC1
Reactant: O=C1c2ccccc2C(=O)N1O
Solvent: C=CCBr
Solvent: CN(C)C=O
Product: C=CCON1C(=O)c2ccccc2C1=O
Reaction time: 0.17 h
Yield: 93.4 %

Procedure:
To a cooled solution (5 to 10° C.) of N-hydroxyphthalimide (53.80 g, 0.33 mol) in DMF (120 mL), was added DBU (46.36 mL, 0.31 mol) was added in one portion, with stirring. After 10 minutes, allyl bromide (25.96 mL, 0.30 mol) was added in portions. The cooling bath was removed and the reaction mixture was stirred at room temperature for 1 hour, until the color turned from dark burgundy to yellow. Ethyl acetate (300 mL) and water (150 mL) were added, the aqueous phase was separated, and the organic phase was washed with water (4×50 mL). The combined aqueous extracts were back-extracted with EtOAc (3×50 mL) and the total EtOAc solution was washed with saturated NaHCO3 (10×50 mL) until the aqueous phase was pale yellow, then with brine (2×75 mL) and dried over anhydrous MgSO4. Removal of the solvent afforded 58.83 g (96% yield) of the product as a white solid.
Reaction SMILES: [NH:1]1[CH:5]=[N:4][C:3]([NH2:6])=[N:2]1.[Si:7]([O:14][CH:15]1[CH2:20][CH2:19][C:18](=O)[CH2:17][CH2:16]1)([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8].C([BH3-])#N.[Na+].O>C(O)(=O)C>[Si:7]([O:14][CH:15]1[CH2:16][CH2:17][CH:18]([NH:6][C:3]2[NH:4][CH:5]=[N:1][N:2]=2)[CH2:19][CH2:20]1)([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8]
Reactant: Nc1nc[nH]n1
Reactant: CC(C)(C)[Si](C)(C)OC1CCC(=O)CC1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: CC(C)(C)[Si](C)(C)OC1CCC(Nc2nnc[nH]2)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 20.8 %

Procedure:
To a solution (30 mL) of 1H-1,2,4-triazol-3-amine (3 g) and 4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexanone (10 g) in acetic acid was added sodium cyanoborohydride (9.3 g), and the mixture was stirred at room temperature for 16 hr. Water was added to the reaction mixture, and the solvent was evaporated under reduced pressure. The obtained residue was poured into saturated aqueous sodium hydrogen carbonate, and the mixture was extracted with a mixed solvent of ethyl acetate and isopropyl alcohol (3:1). The obtained extract was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound as a colorless solid (2.2 g, 20%).
Reaction SMILES: [CH3:1][N:2]([CH3:30])[CH2:3][CH2:4][CH2:5][NH:6][C:7]1[CH:12]=[C:11]([CH:13](O)[C:14]2[CH:19]=[CH:18][C:17]([NH:20]C(=O)OC(C)(C)C)=[CH:16][C:15]=2[F:28])[CH:10]=[CH:9][N:8]=1.Cl>CO.[Pd]>[NH2:20][C:17]1[CH:18]=[CH:19][C:14]([CH2:13][C:11]2[CH:10]=[CH:9][N:8]=[C:7]([NH:6][CH2:5][CH2:4][CH2:3][N:2]([CH3:1])[CH3:30])[CH:12]=2)=[C:15]([F:28])[CH:16]=1
Reactant: CN(C)CCCNc1cc(C(O)c2ccc(NC(=O)OC(C)(C)C)cc2F)ccn1
Agent: [Pd]
Agent: Cl
Solvent: CO
Product: CN(C)CCCNc1cc(Cc2ccc(N)cc2F)ccn1
Temperature: 75 °C
Yield: 54 %

Procedure:
To a solution of tert-butyl 4-((2-(3-(dimethylamino)propylamino)pyridine-4-yl)(hydroxy)methyl)-3-fluorophenylcarbamate (80 mg, 0.19 mmol) in MeOH (5.0 mL) was added 2 mL of conc. HCl and palladium on charcoal (10%, 200 mg). The suspension was heated at 75° C. under H2 atmosphere for 24 h. The mixture was cooled down, filtered and concentrated in vacuo. The residue was dissolved in 1 mL of conc. NH4OH and it was extracted with DCM (5×5 mL). The combined organic layer was dried over Na2SO4. After filtration, it was concentrated in vacuo to give 4-(4-amino-2-fluorobenzyl)-N-(3-(dimethylamino)propyl)pyridin-2-amine (31 mg, 40% yield). MS (ESI+): m/z 303.31 (M+H)+.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH:16]([C:22](=O)[CH2:23][CH2:24][CH3:25])[C:17](OCC)=[O:18])=[CH:11][CH:10]=1)#[N:2].[CH2:27]([O:30][CH:31]1[CH2:36][CH2:35][CH:34]([NH:37][C:38]2[NH:42][CH:41]=[N:40][N:39]=2)[CH2:33][CH2:32]1)[CH:28]=[CH2:29]>>[O:18]=[C:17]1[C:16]([CH2:15][C:12]2[CH:13]=[CH:14][C:9]([C:4]3[C:3]([C:1]#[N:2])=[CH:8][CH:7]=[CH:6][CH:5]=3)=[CH:10][CH:11]=2)=[C:22]([CH2:23][CH2:24][CH3:25])[N:39]2[N:40]=[CH:41][N:42]=[C:38]2[N:37]1[CH:34]1[CH2:33][CH2:32][CH:31]([O:30][CH2:27][CH:28]=[CH2:29])[CH2:36][CH2:35]1
Reactant: C=CCOC1CCC(Nc2nnc[nH]2)CC1
Reactant: CCCC(=O)C(Cc1ccc(-c2ccccc2C#N)cc1)C(=O)OCC
Product: C=CCOC1CCC(n2c(=O)c(Cc3ccc(-c4ccccc4C#N)cc3)c(CCC)n3ncnc23)CC1
Temperature: 250 °C
Reaction time: 0.33 h
Yield: 23.6 %

Procedure:
A mixture of ethyl 2-[(2′-cyanobiphenyl-4-yl)methyl]-3-oxohexanoate (4 g) and N-[4-(prop-2-en-1-yloxy)cyclohexyl]-4H-1,2,4-triazol-3-amine (1.3 g) was stirred at 250° C. for 20 min under microwave irradiation. The obtained reaction mixture was purified by silica gel column chromatography to give the title compound as a colorless solid (0.7 g, 24%).
Reaction SMILES: [F:1][C:2]1[CH:24]=[C:23]([N+:25]([O-:27])=[O:26])[CH:22]=[CH:21][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12](C3C=CC(O)=CC=3)[S:13][C:6]=12.[OH:28][C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1>>[F:1][C:2]1[CH:24]=[C:23]([N+:25]([O-:27])=[O:26])[CH:22]=[CH:21][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:33]3[CH:34]=[C:29]([OH:28])[CH:30]=[CH:31][CH:32]=3)[S:13][C:6]=12
Reactant: O=[N+]([O-])c1ccc(Oc2ccnc3cc(-c4ccc(O)cc4)sc23)c(F)c1
Reactant: OB(O)c1cccc(O)c1
Product: O=[N+]([O-])c1ccc(Oc2ccnc3cc(-c4cccc(O)c4)sc23)c(F)c1
Yield: 66 %

Procedure:
Starting from the nitrobromo compound 42, following the procedure described above for the synthesis of compound 153 (scheme 28, example 109) but substituting 4-hydroxyphenylboronic acid for 3-hydroxyphenylboronic acid, title compound 160 was obtained in 66% yield as a gray solid. LRMS (M+1) 383.1 (100%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]([CH3:14])([CH3:13])[C:10](O)=[O:11])[CH:5]=[C:6]([Cl:8])[CH:7]=1.C(Cl)[Cl:16]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]([CH3:14])([CH3:13])[C:10]([Cl:16])=[O:11])[CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: ClCCl
Reactant: CC(C)(C(=O)O)c1cc(Cl)cc(Cl)c1
Solvent: CN(C)C=O
Product: CC(C)(C(=O)Cl)c1cc(Cl)cc(Cl)c1
Reaction time: 12 h

Procedure:
To a solution of 8.3 g (35.6 mmol) 2-(3,5-dichloro-phenyl)-2-methyl-propionic acid in 80 ml CH2Cl2 and 4 drops DMF 6.1 ml (71.2 mmol) oxalyl chloride was added at 0° C. and the resulting mixture stirred for 12 h After evaporation of the solvent 8.3 g (93%) 2-(3,5-dichloro-phenyl)-2-methyl-propionyl chloride was obtained as a light yellow oil, which was used without further purification.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6](Cl)=[O:7].C1COCC1.[C:14]([C:16]1[CH:17]=[C:18]([NH2:22])[CH:19]=[CH:20][CH:21]=1)#[CH:15]>CCN(CC)CC>[C:14]([C:16]1[CH:17]=[C:18]([NH:22][C:6]([C:2]2[S:1][CH:5]=[CH:4][CH:3]=2)=[O:7])[CH:19]=[CH:20][CH:21]=1)#[CH:15]
Reactant: C#Cc1cccc(N)c1
Reactant: O=C(Cl)c1cccs1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: C#Cc1cccc(NC(=O)c2cccs2)c1
Temperature: 55 °C
Yield: 85 %

Procedure:
A dry 25 mL flask was charged with thiophene-2-carbonyl chloride and THF (5 mL) was added. 3-Ethynyl-phenylamine (0.905 g, 3.59 mmol) was added to the THF solution of the acid chloride followed by NEt3, and the mixture was allowed to stir at 55° C. The reaction mixture was then allowed to cool to room temperature and extracted with EtOAc (˜10 mL), 1M HCl (˜10 mL), followed by brine (˜10 mL). The combined organic extracts were combined and dried over anhydrous Na2SO4(s) and the concentrated. The crude residue was purified by chromatography (silica gel, gradient elution EtOAc/Hexanes 0 to 50%). The product containing fractions were concentrated to give the title compound as a tan solid (0.33 mg, 1.45 mmol, 85%).
Reaction SMILES: [O:1]=[C:2]1[C:11]([CH:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][CH:21]([CH2:24][C:25]3[CH:33]=[C:32]([CH3:34])[C:31]4[C:27](=[CH:28][N:29]([CH2:35][O:36][CH3:37])[N:30]=4)[CH:26]=3)[CH2:22][OH:23])=[O:19])[CH2:14][CH2:13]2)=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[NH:3]1.C(N(CC)CC)C>CS(C)=O>[O:1]=[C:2]1[C:11]([CH:12]2[CH2:13][CH2:14][N:15]([C:18]([O:20][C@H:21]([CH2:24][C:25]3[CH:33]=[C:32]([CH3:34])[C:31]4[C:27](=[CH:28][N:29]([CH2:35][O:36][CH3:37])[N:30]=4)[CH:26]=3)[CH:22]=[O:23])=[O:19])[CH2:16][CH2:17]2)=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[NH:3]1
Reactant: COCn1cc2cc(CC(CO)OC(=O)N3CCC(c4cc5ccccc5[nH]c4=O)CC3)cc(C)c2n1
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Product: COCn1cc2cc(C[C@H](C=O)OC(=O)N3CCC(c4cc5ccccc5[nH]c4=O)CC3)cc(C)c2n1
Temperature: 5 °C
Reaction time: 0.02 h

Procedure:
1-Hydroxy-3-(2-(methoxymethyl)-7-methyl-2H-indazol-5-yl)propan-2-yl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate (0.65 g, 1.29 mmol) was dissolved in anhydrous dimethyl sulfoxide (5.0 mL). Triethylamine (0.54 mL, 3.87 mmol) was added and the reaction mixture cooled to ca. 5° C. using an ice bath. A solution of sulfur trioxide pyridine complex (0.62 g, 3.87 mmol) in dimethyl sulfoxide (4.0 mL) was added in one portion. After 1 min, the ice bath was removed and the reaction mixture stirred at room temperature for 20 min. The reaction mixture was poured into an ice slurry and extracted with ethyl acetate (3×). The combined organic extracts were washed with 10% citric acid (2×), water (2×), 5% sodium bicarbonate (2×), brine (2×), dried over sodium sulfate, and concentrated. Column chromatography afforded 0.55 g (85%). 1H-NMR (DMSO. d6, 500 MHz) δ 1.90 (s, 3H), 2.48 (s, 3H), 2.51 (m, 2H), 2.71-2.95 (m, 4H), 4.51 (m, 1H), 4.72-4.84 (m, 1H), 6.31-6.46 (m, 1H), 6.91 (d, J=4.0, 1H), 8.36 (s, 1H), 11.74 (s, 1H). Mass spec.: 503.3 (MH)+.
Reaction SMILES: Br[C@H:2]1[CH2:6][O:5][C@@H:4]([CH2:7][S:8]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)(=[O:10])=[O:9])[CH2:3]1.[C:18]([O-:21])(=[S:20])[CH3:19].[K+]>C(#N)C>[F:17][C:14]1[CH:15]=[CH:16][C:11]([S:8]([CH2:7][C@@H:4]2[O:5][CH2:6][C@@H:2]([S:20][C:18](=[O:21])[CH3:19])[CH2:3]2)(=[O:10])=[O:9])=[CH:12][CH:13]=1
Reactant: O=S(=O)(C[C@H]1C[C@@H](Br)CO1)c1ccc(F)cc1
Reactant: CC([O-])=S
Agent: [K+]
Solvent: CC#N
Product: CC(=O)S[C@@H]1CO[C@@H](CS(=O)(=O)c2ccc(F)cc2)C1
Yield: 55.8 %

Procedure:
The title compound is prepared by the procedure of Example 5 using 0.969 g of product from Example 30, 0.360 g of potassium thioacetate, and 9 ml of acetonitrile to give 0.533 g of the desired product.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][C:9](OCC2C=CC=CC=2)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:19][N:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:22]([CH2:29][C@H:30]([NH2:33])[CH2:31][OH:32])=[CH:21]1>ClC1C=CC=CC=1>[CH3:19][N:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:22]([CH2:29][C@H:30]2[CH2:31][O:32][C:9]([CH2:8][CH2:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[N:33]2)=[CH:21]1
Reactant: Cn1cc(C[C@H](N)CO)c2ccccc21
Reactant: O=C(CCc1ccccc1)OCc1ccccc1
Solvent: Clc1ccccc1
Product: Cn1cc(C[C@H]2COC(CCc3ccccc3)=N2)c2ccccc21
Yield: 76 %

Procedure:
Under an argon atmosphere, a mixture of benzyl 3-phenylpropionate (1.5 mmol), (S)-2-(N-methylindol-3-ylmethyl)-2-aminoethanol (1.5 mmol), Zn4(OCOCF3)6O (0.15 mmol) and chlorobenzene (2.5 mL) was heated under reflux for 18 hours. From the resulting solution, the solvent was removed using an evaporator, and the residues were purified by silica gel column chromatography to give (S)-4-(N-methylindol-3-ylmethyl)-2-(2-phenylethyl)-1,3-oxazoline in 76% yield. The compound was identified by comparison with physical property data of the known compound.
Reaction SMILES: [NH4+].[Cl-].[N:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][C:11]=2[NH:13][S:14]([C:17]2[C:22]([N+:23]([O-])=O)=[CH:21][CH:20]=[CH:19][N:18]=2)(=[O:16])=[O:15])[CH:6]=[CH:5][CH:4]=1.C1COCC1>CO.[Zn]>[N:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][C:11]=2[NH:13][S:14]([C:17]2[C:22]([NH2:23])=[CH:21][CH:20]=[CH:19][N:18]=2)(=[O:16])=[O:15])[CH:6]=[CH:5][CH:4]=1
Reactant: O=[N+]([O-])c1cccnc1S(=O)(=O)Nc1cccc2cccnc12
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: C1CCOC1
Solvent: CO
Product: Nc1cccnc1S(=O)(=O)Nc1cccc2cccnc12
Temperature: 25 °C
Reaction time: 18 h
Yield: 95.1 %

Procedure:
Sat. NH4Cl (0.49 g, 9.09 mmol) was added to a solution of 3-nitro-pyridine-2-sulfonic acid quinolin-8-ylamide (Intermediate 259) (0.3 g, 0.91 mmol) in MeOH:THF(10 ml, 1:1) followed by zinc powder (0.48 g, 7.27 mmol) and the mixture was stirred at room temperature for 18 h. The mixture was filtered through celite and washed with THF. The filtrate was concentrated in vacuo and the residue was diluted with EtOAc. The organic phase was dried (Na2SO4) and concentrated in vacuo. The crude residue was purified by column chromatography with DCM/MeOH as the eluent to give the title compound (0.26 g, 95%)
Reaction SMILES: [C:1]([O:4][C@H:5]1[C@@H:14]2[O:15]C(C)(C)[O:17][C@@:13]32[C@H:8]([C@H:9]([C:21]2[N:22]=[C:23]([CH2:26][CH3:27])[S:24][CH:25]=2)[CH2:10][CH2:11][C@H:12]3[CH3:20])[CH:7]=[C:6]1[CH3:28])(=[O:3])[CH3:2]>C1(C)C=CC(S(O)(=O)=O)=CC=1>[C:1]([O:4][C@@H:5]1[C:6]([CH3:28])=[CH:7][C@@H:8]2[C@:13]([OH:17])([C@H:12]([CH3:20])[CH2:11][CH2:10][C@H:9]2[C:21]2[N:22]=[C:23]([CH2:26][CH3:27])[S:24][CH:25]=2)[C@H:14]1[OH:15])(=[O:3])[CH3:2]
Reactant: CCc1nc([C@@H]2CC[C@@H](C)[C@]34OC(C)(C)O[C@H]3[C@H](OC(C)=O)C(C)=C[C@@H]24)cs1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Product: CCc1nc([C@@H]2CC[C@@H](C)[C@]3(O)[C@@H](O)[C@H](OC(C)=O)C(C)=C[C@@H]23)cs1
Yield: 30.2 %

Procedure:
A solution of (3aS,4R,6aS,7R,10R,10aR)-7-(2-ethyl-1,3-thiazol-4-yl)-2,2,5,10-tetramethyl-4,6a,7,8,9,10-hexahydro-3aH-naphtho[1,8a-d][1,3]dioxol-4-yl acetate (Preparation 165, 345 mg) in methanolic para-toluenesulfonic acid (1% w/w, 10 ml) was stirred at room temperature for 12 days. The reaction mixture was partitioned between ethyl acetate and a mixture of dilute aqueous sodium chloride and saturated aqueous sodium hydrogen carbonate. The organic phase was dried (MgSO4), evaporated and purified by flash column chromatography on silica gel using a gradient elution ethyl acetate:hexane (1:5 to 1:1) to give the product as a gum (94 mg).
Reaction SMILES: [C:1](Cl)(Cl)=[O:2].[NH2:5][C:6]12[CH2:15][CH:10]3[CH2:11][CH:12]([CH2:14][C:8]([N+:16]([O-:18])=[O:17])([CH2:9]3)[CH2:7]1)[CH2:13]2>C1(C)C=CC=CC=1>[N:5]([C:6]12[CH2:13][CH:12]3[CH2:11][CH:10]([CH2:9][C:8]([N+:16]([O-:18])=[O:17])([CH2:14]3)[CH2:7]1)[CH2:15]2)=[C:1]=[O:2]
Reactant: NC12CC3CC(C1)CC([N+](=O)[O-])(C3)C2
Reactant: O=C(Cl)Cl
Solvent: Cc1ccccc1
Product: O=C=NC12CC3CC(C1)CC([N+](=O)[O-])(C3)C2
Reaction time: 6 h
Yield: 90 %

Procedure:
10 mmole of 1-amino-3-nitroadamantane obtained by the method of Example 66 was dissolved in toluene (100 ml). To the resultant solution, 12 mmole of phosgene was added at the room temperature and stirred for 6 hours. As a result, The conversion of 1-amino-3-nitroadamantane was 99%, and 1-isocyanato-3-nitroadamantane (yield 90%) was formed.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[CH3:9][CH2:10][O-:11].[Na+].CCO>CCO>[Cl:1][C:2]1[N:7]=[C:6]([O:11][CH2:10][CH3:9])[CH:5]=[CH:4][N:3]=1
Reactant: CC[O-]
Reactant: Clc1ccnc(Cl)n1
Agent: [Na+]
Solvent: CCO
Product: CCOc1ccnc(Cl)n1
Reaction time: 1 h
Yield: 75.6 %

Procedure:
To a solution of 2,4-dichloropyrimidine (Aldrich, 10.0 g, 67.12 mmol) in abs. EtOH (120 mL) at -3° C. under nitrogen atmosphere was slowly added (over 2 hours) 1M NaOEt/EtOH (68 mL, 68 mmol) and the resulting mixture stirred for 1 hour. Solvent was evaporated in vacuo and the residue partitioned between H2O and Et2O. The aqueous phase was extracted with Et2O and the combined organic phase was washed with brine, dried (Na2SO4) and evaporated (water aspirator pump, 35° C.). The resulting residue was filtered and washed with petroleum ether to provide the desired product (8.05 g, 75%) as a yellowish solid: mp 30-31° C. (lit. 35° C.); 1H NMR (CDCl3): δ1.40 (t, J=7.2 Hz, 3H), 4.44 (quartet, J=7.2 Hz, 2H), 6.62 (d, J=5.7 Hz, 1H), 8.27 (d, J=5.7 Hz, 1H); MS m/z 161 (M+3, 34%), 159 (M+1, 100%). Anal. Calcd. for C6H7ClN2O: C, 45.44; H, 4.45; N, 17.66; Cl, 22.36. Found: C, 45.32; H, 4.41; N, 17.60; Cl, 22.43.
Reaction SMILES: [C:1]1([N:7]2[C:11]([CH2:12][CH2:13][CH:14]=O)=[CH:10][C:9]([CH2:16][CH3:17])=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:18]1([N:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.CCN(C(C)C)C(C)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[C:18]1([N:24]2[CH2:29][CH2:28][N:27]([CH2:14][CH2:13][CH2:12][C:11]3[N:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[N:8]=[C:9]([CH2:16][CH3:17])[CH:10]=3)[CH2:26][CH2:25]2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: CCc1cc(CCC=O)n(-c2ccccc2)n1
Reactant: c1ccc(N2CCNCC2)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Product: CCc1cc(CCCN2CCN(c3ccccc3)CC2)n(-c2ccccc2)n1

Procedure:
41 mg (80%) of target compound was obtained by using a method same as in Example 1 by using 3-(1-phenyl-3-ethyl-1H-pyrazol-5-yl)propanal (31 mg, 0.138 mmol), 1-phenylpiperazine (0.021 mL, 0.138 mmol), DIPEA (0.036 mL, 0.206 mmol) and NaBH(OAc)3 (88 mg, 0.414 mmol).
Reaction SMILES: [H-].[Na+].[CH3:3][N:4]1[C:8]([CH3:9])=[CH:7][C:6]([C:10]([O:12][CH3:13])=[O:11])=[C:5]1[CH2:14][C:15]([O:17][CH3:18])=[O:16].[CH:19](OC)=[O:20].CO>O1CCCC1>[CH:19]([CH:14]([C:5]1[N:4]([CH3:3])[C:8]([CH3:9])=[CH:7][C:6]=1[C:10]([O:12][CH3:13])=[O:11])[C:15]([O:17][CH3:18])=[O:16])=[O:20]
Reactant: COC(=O)Cc1c(C(=O)OC)cc(C)n1C
Reactant: COC=O
Agent: [H-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: COC(=O)c1cc(C)n(C)c1C(C=O)C(=O)OC
Temperature: 10 °C

Procedure:
Sodium hydride (2.29 g, 60% dispersion in mineral oil) was added portionwise to a stirred solution of methyl 1,5-dimethyl-2-[2-(methyloxy)-2-oxoethyl]-1H-pyrrole-3-carboxylate (2.37 g) in tetrahydrofuran (30 ml) at 20° C. After fifteen minutes the reaction mixture was cooled to 10° C. and methyl formate (1.0 ml) added. After ten minutes a mixture of methanol (0.05 ml) and tetrahydrofuran (1 ml) was added. The reaction mixture was stirred at room temperature for sixteen hours. After cooling to 10° C., methanol (0.1 ml) was added, the mixture was stirred at room temperature for two hours. After cooling in an ice bath, methanol (8.4 ml) was added dropwise, the mixture was stirred for a further fifteen minutes, then evaporated. The residue was partitioned between ethyl acetate and aqueous ammonium chloride, and then acidified by addition of 5N hydrochloric acid. The aqueous phase was extracted with a second portion of ethyl acetate. The combined organic extracts were washed with water, then brine, dried (MgSO4) and evaporated. The solid residue washed with hexane and then dried to give the title compound 2.59 g as a tautomeric mixture.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([N:15]([CH3:17])[CH3:16])([CH3:14])[C:11](O)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8].[H-].[Al+3].[Li+].[H-].[H-].[H-].O1CCCC1.[H-]>C1(C)C=CC=CC=1>[CH3:14][C:10]([N:15]([CH3:17])[CH3:16])([CH2:11][OH:12])[CH2:9][C:4]1[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=1
Reactant: CN(C)C(C)(Cc1ccc(Cl)c(Cl)c1)C(=O)O
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CN(C)C(C)(CO)Cc1ccc(Cl)c(Cl)c1

Procedure:
1.65 to 1.75 mol of amino ester (II) are reduced in toluene with a lithium aluminium hydride-tetrahydrofuran addition complex prepared starting from 1 mol of hydride, to obtain (+/-)3-(3,4-dichlorophenyl)-2-dimethylamino-2-methylpropan-1-ol (I) or cericlamine which is optionally salified with hydrochloric acid.
Reaction SMILES: [H-].[Na+].[OH:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH:7]=[O:8].[CH3:12][S:13][CH2:14][CH2:15]Cl>CN(C=O)C>[CH3:12][S:13][CH2:14][CH2:15][O:3][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH:7]=[O:8]
Reactant: O=Cc1cccc(O)c1
Reactant: CSCCCl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CSCCOc1cccc(C=O)c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
NaH (1.3 g, 54 mmol) is added to a solution of 5.0 g (41 mmol) 3-hydroxybenzaldehyde in 30 ml DMF at 0° C. After stirring for 1 h 4.44 ml (45 mmol) 2-chloroethyl methyl sulphide is added. The reaction mixture is warmed to room temperature and stirring is continued for 16 h. Then the reaction mixture is poured onto water and extracted with ethyl acetate. The combined organic layers are washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue is purified by flash-chromatography on silica gel (hexane/EtOAc=3:1) to afford the title compound as a colorless oil.