Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1](=[CH:8][C:9](=[O:11])[CH3:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O1CCCC1>CO>[C:2]1([CH:1]=[CH:8][CH:9]([OH:11])[CH3:10])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(=O)C=Cc1ccccc1
Solvent: CO
Solvent: C1CCOC1
Product: CC(O)C=Cc1ccccc1
Yield: 34.1 %

Procedure:
In a 200 ml stainless steel autoclave were charged 5 g (34.2 mmole) of benzalacetone and 0.213 g (0.171 mmole) of ##STR24## synthesized in Example 4, and 3 ml of tetrahydrofuran and 2 ml of methanol were added thereto, followed by allowing the mixture to react at 30° C. under a hydrogen pressure of 50 kg/cm2 for 45 hours. The solvent was removed by distillation under reduced pressure (10 mmHg), and the reaction product was analyzed by GLC (PEG HT, 25 m, produced by Gasukuro Kogyo K.K.) to find the conversion to be 34.5%. The product was separated into the unreacted ketone and the hydrogenation product by silica gel column chromatography (eluent: hexane/ethyl acetate=4/1 by volume) to obtain 1.73 g of 4-phenyl-3-buten-2-ol having a purity of 89%. [α]D25 : +18.1° (c=5, CS2).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:11](=[O:12])[N:10]2[CH:13]=[CH:14][CH:15]=[C:16]([SH:17])[C:9]2=[N:8][CH:7]=1)=[O:5])[CH3:2].[CH3:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]=[C:26]=[O:27])=[CH:21][CH:20]=1>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[C:11](=[O:12])[N:10]2[CH:13]=[CH:14][CH:15]=[C:16]([S:17][C:26](=[O:27])[NH:25][C:22]3[CH:23]=[CH:24][C:19]([CH3:18])=[CH:20][CH:21]=3)[C:9]2=[N:8][CH:7]=1)=[O:5])[CH3:2]
Reactant: Cc1ccc(N=C=O)cc1
Reactant: CCOC(=O)c1cnc2c(S)cccn2c1=O
Solvent: ClCCl
Product: CCOC(=O)c1cnc2c(SC(=O)Nc3ccc(C)cc3)cccn2c1=O

Procedure:
To a suspension of 0.4 g of 3-ethoxycarbonyl-9-mercapto-4H-pyrido[1,2-a]pyrimidin-4-one II-1 in 10 ml of dry CH2Cl2 is added 0.35 g of 4-methylphenyl isocyanate III-1, and the resultant mixture is stirred at room temperature for 4 hours. At this time the reaction mixture is crystallized again after it is once dissolved.
Reaction SMILES: CSC.B.[C:5]([O:9][C:10]([N:12]1[CH2:16][C@@H:15]([O:17][C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=2)[CH2:14][C@H:13]1[C:28](O)=[O:29])=[O:11])([CH3:8])([CH3:7])[CH3:6].O>C1COCC1>[C:5]([O:9][C:10]([N:12]1[CH2:16][C@@H:15]([O:17][C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=2)[CH2:14][C@H:13]1[CH2:28][OH:29])=[O:11])([CH3:8])([CH3:7])[CH3:6]
Reactant: CC(C)(C)OC(=O)N1C[C@@H](Oc2ccc3ccccc3c2)C[C@H]1C(=O)O
Agent: B
Solvent: C1CCOC1
Solvent: O
Solvent: CSC
Product: CC(C)(C)OC(=O)N1C[C@@H](Oc2ccc3ccccc3c2)C[C@H]1CO
Temperature: 0 °C
Yield: 102.3 %

Procedure:
Borane-dimethyl sulfide (0.63 ml, 6.3 mmol) was added to a solution of (2S,4S)-1-tert-butoxycarbonyl-4-(2-naphthyloxy)-2-pyrrolidinylcarboxylic acid (1.12 g, 3.13 mmol) in THF (30 ml) under stirring at 0° C. The reaction mixture was stirred at 50° C. for 1.5 hours. After the reaction mixture was cooled to 0° C., water (20 ml) was added thereto. The mixture was then extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate and distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column (silica gel: 50 g), whereby from chloroform/methanol (50/1) eluate fractions, the title compound (1.10 g, 100%) was obtained as a pale yellow oil.
Reaction SMILES: Cl[C:2]1[CH:25]=[C:24]([F:26])[C:23]([F:27])=[CH:22][C:3]=1[C:4]([C:6](=[CH:12][NH:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=1[F:21])[C:7]([O:9][CH2:10][CH3:11])=[O:8])=[O:5].[H-].[Na+].O>O1CCCC1>[F:21][C:15]1[CH:16]=[C:17]([F:20])[CH:18]=[CH:19][C:14]=1[N:13]1[C:2]2[C:3](=[CH:22][C:23]([F:27])=[C:24]([F:26])[CH:25]=2)[C:4](=[O:5])[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:12]1
Reactant: CCOC(=O)C(=CNc1ccc(F)cc1F)C(=O)c1cc(F)c(F)cc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CCOC(=O)c1cn(-c2ccc(F)cc2F)c2cc(F)c(F)cc2c1=O
Reaction time: 0.5 h
Yield: 82.9 %

Procedure:
The solution of 3.0 g of ethyl 2-(2-chloro-4,5-difluorobenzoyl)-3-(2,4-difluorophenylamino)acrylate in 30 ml of anhydrous tetrahydrofuran was cooled to 10° C. 0.3 g (1.02 eq.) of 60% sodium hydride was added to the reaction mixture, which was refluxed for 4.5 hours. The reaction mixture was cooled to 5˜10° C. 54.6 ml of water was added to the reaction mixture, which was then stirred for 30 minutes. The organic layer was filtered under a reduced pressure and washed with a mixed solution of n-hexane and ether (1/1). The resulting wet cake was dried under a reduced pressure at 40˜45° C. for 6 hours to give 2.26 g of ethyl 1-(2,4-difluorophenyl)-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate (Yield: 82.8%).
Reaction SMILES: F[C:2]1[N:29]=[CH:28][C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH:10][C:11]3[CH:12]=[C:13]4[C:17](=[CH:18][CH:19]=3)[N:16]([CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=3)[N:15]=[CH:14]4)[C:4]=2[CH:3]=1.[CH3:30][O:31][C:32]1[CH:39]=[CH:38][C:35]([CH2:36][NH2:37])=[CH:34][CH:33]=1>CS(C)=O>[F:27][C:23]1[CH:22]=[C:21]([CH:26]=[CH:25][CH:24]=1)[CH2:20][N:16]1[C:17]2[C:13](=[CH:12][C:11]([NH:10][C:9]3[C:4]4[CH:3]=[C:2]([NH:37][CH2:36][C:35]5[CH:38]=[CH:39][C:32]([O:31][CH3:30])=[CH:33][CH:34]=5)[N:29]=[CH:28][C:5]=4[N:6]=[CH:7][N:8]=3)=[CH:19][CH:18]=2)[CH:14]=[N:15]1
Reactant: COc1ccc(CN)cc1
Reactant: Fc1cccc(Cn2ncc3cc(Nc4ncnc5cnc(F)cc45)ccc32)c1
Solvent: CS(C)=O
Product: COc1ccc(CNc2cc3c(Nc4ccc5c(cnn5Cc5cccc(F)c5)c4)ncnc3cn2)cc1
Temperature: 69 °C
Reaction time: 165 h
Yield: 60.9 %

Procedure:
A mixture of compound 202 (3.00 g, 7.73 mmol) and 4-methoxybenzylamine (10.2 mL, 77.3 mmol) in dry DMSO (18 mL) was stirred under a nitrogen atmosphere at 68-70° C. (bath temperature) for 165 h. The solution was then cooled and petroleum ether (200 mL) was added. It was stirred at room temperature for 15 min. The layers were allowed to separate and the petroleum ether layer was decanted. This procedure was repeated with more petroleum ether (200 ml). Water (200 mL) was added and the mixture was stirred at room temperature for 45 min. The oil was deposited. Thus, the product was extracted into ethyl acetate; dried (MgSO4) and solvent removed to give a brown oil. It was purified by a silica column (EtOAc/petroleum ether: gradient from 30% to pure EtOAc) to give pure N4-(1-(3-fluorobenzyl)-1H-indazol-5-yl)-N6-(4-methoxybenzyl)pyrido[3,4-d]pyrimidine-4,6-diamine (211) (2.38 g, 61%) as a yellow/orange solid, mp 196-198° C.; 1H NMR δ [(CD3)2SO] 9.75 (s, 1H), 8.72 (s, 1H), 8.29 (s, 1H), 8.22 (poorly resolved d, J=1.3 Hz, 1H), 8.15 (d, J=0.7 Hz, 1H), 7.73 (br d, J=9.0 Hz, 1H), 7.68 (dd, J=9.0, 1.8 Hz, 1H), 7.40-7.31 (m, 3H), 7.24-7.17 (m, 2H), 7.13-7.01 (m, 3H), 6.92-6.84 (m, 2H), 5.70 (s, 2H) 4.49 (d, J=6.3 Hz, 2H), 3.71 (s, 3H). Anal. Calcd for C29H24FN7O.1.5H2O: C, 65.40; H, 5.11; N, 18.41%. Found C, 65.45; H, 5.07; N, 18.58%.
Reaction SMILES: C(N(CC)CC)C.[NH2:8][C@@H:9]([CH2:12][CH3:13])[CH2:10][OH:11].[N+:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[S:23](Cl)(=[O:25])=[O:24])([O-:16])=[O:15].C(=O)([O-])O.[Na+]>O1CCCC1>[OH:11][CH2:10][C@@H:9]([NH:8][S:23]([C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[N+:14]([O-:16])=[O:15])(=[O:24])=[O:25])[CH2:12][CH3:13]
Reactant: CC[C@H](N)CO
Reactant: O=[N+]([O-])c1ccccc1S(=O)(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC[C@@H](CO)NS(=O)(=O)c1ccccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 99.1 %

Procedure:
Triethylamine (0.94 ml, 6.74 mmol) was added to a solution of 400 mg (4.49 mmol) of (S)-2-aminobutan-1-ol in tetrahydrofuran (5 ml), and the mixture was stirred at room temperature for 10 min. 2-Nitrobenzenesulfonyl chloride (995.1 mg, 4.49 mmol) was added to the solution, and the mixture was stirred at room temperature for 15 min. A saturated aqueous sodium hydrogencarbonate solution was added thereto to stop the reaction, and the reaction solution was then extracted with ethyl acetate, was dried over anhydrous sodium sulfate, and was filtered. The filtrate was concentrated under the reduced pressure, and the residue was purified by column chromatography on silica gel (hexane:ethyl acetate=2:1) to give 1.22 g (yield 99%) of the title compound.
Reaction SMILES: C([Li])CCC.C(NC(C)C)(C)C.CN(P(N(C)C)(N(C)C)=O)C.[CH:24]1([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:27][CH2:26][CH2:25]1.Cl[CH2:34][O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>C1COCC1.O>[CH2:36]([O:35][CH2:34][C:24]1([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:27][CH2:26][CH2:25]1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1
Reactant: CCOC(=O)C1CCC1
Reactant: ClCOCc1ccccc1
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: CCOC(=O)C1(COCc2ccccc2)CCC1
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
n-Butyl lithium solution (2.20M in hexane, 23.2 ml, 51 mmol) was added via a syringe under nitrogen to a stirred solution of di-i-propylamine (5.13 g, 51 mmol) and HMPA (3.5 ml, 20 mmol) in THF (100 ml) at 0° C. The resulting mixture was stirred at 0° C. for 10 minutes, cooled to -78° C., added a solution of ethyl cyclobutanecarboxylate (5 g, 39 mmol) in THF (10 ml) via a dropping funnel. The resulting mixture was stirred at -78° C. for 0.5 hour, then warmed to 0° C. and stirred for 0.5 hour. The mixture was recooled to -78° C., treated with a solution of benzyl chloromethyl ether (6.58 g, 42 mmol) in THF (10 ml). The resulting mixture was stirred at -78° C. for 20 minutes, slowly warmed to room temperature and stirred for 1 hour. It was poured into cold water, extracted with diethyl ether. The ethereal extract was washed successively with diluted HCl, 5% NaHCO3, dried, filtered and evaporated to give a residue. This residue was purified by distillation to afford the desired product as a pale yellow oil: bp 102°-3° C. (0.02 mm); NMR (CDCl3) δ=1.23 (3H, t, J=7 Hz), 1.6~2.6 (6H, m), 3.68 (2H, s), 4.15 (2H, q, J=7 Hz), 4.53 (2H, s), 7.30 (5H, s).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([S:8](Cl)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.[NH2:12][C:13]1[CH:14]=[C:15]([CH:19]2[CH2:28][C:27]([CH3:30])([CH3:29])[C:26]3[C:21](=[CH:22][CH:23]=[C:24]([C:31]#[N:32])[CH:25]=3)[NH:20]2)[CH:16]=[CH:17][CH:18]=1.N1C=CC=CC=1>ClCCl>[C:31]([C:24]1[CH:25]=[C:26]2[C:21](=[CH:22][CH:23]=1)[NH:20][CH:19]([C:15]1[CH:14]=[C:13]([NH:12][S:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)(=[O:10])=[O:9])[CH:18]=[CH:17][CH:16]=1)[CH2:28][C:27]2([CH3:30])[CH3:29])#[N:32]
Reactant: CC1(C)CC(c2cccc(N)c2)Nc2ccc(C#N)cc21
Reactant: O=S(=O)(Cl)c1cccc(F)c1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC1(C)CC(c2cccc(NS(=O)(=O)c3cccc(F)c3)c2)Nc2ccc(C#N)cc21
Reaction time: 8 h
Yield: 43.4 %

Procedure:
3-Fluoro-benzenesulfonyl chloride (116 mg, 0.59 mmol) was added dropwise to a mixture of 2-(3-amino-phenyl)-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carbonitrile (150 mg, 0.54 mmol) and pyridine (65 mg, 0.81 mmol) in dichloromethane (5 mL). The resultant mixture was allowed to stir overnight. The reaction mixture was washed by water, dried over magnesium sulfate. It was filtered and concentrated to provide the crude product. It was purified by column chromatography (silica gel, petroleum ether:ethyl acetate=5:1) to afford N-[3-(6-cyano-4,4-dimethyl-1,2,3,4-tetrahydro-quinolin-2-yl)-phenyl]-3-fluoro-benzenesulfonamide as off-white solid (102 mg, yield: 42.5%). MS (ESI+APCI) M+1=436.1.
Reaction SMILES: [Br:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[CH:4][CH:3]=1.[Cl:9][CH2:10][CH2:11][N:12]=[C:13]=[O:14]>C1COCC1>[Br:1][C:2]1[N:7]=[C:6]([NH:8][C:13]([NH:12][CH2:11][CH2:10][Cl:9])=[O:14])[CH:5]=[CH:4][CH:3]=1
Reactant: Nc1cccc(Br)n1
Reactant: O=C=NCCCl
Solvent: C1CCOC1
Product: O=C(NCCCl)Nc1cccc(Br)n1
Temperature: 25 °C
Reaction time: 18 h
Yield: 66 %

Procedure:
To a solution of 6-bromo-2-pyridinamine (1 g, 5.78 mmol) in anh. THF (25 mL), at r.t., under N2, was added 1-chloro-2-isocyanatoethane (1.2 mL, 2.5 eq) and the reaction mixture was stirred at r.t. for 18 hr. The crude mixture was partitioned between CH2Cl2 and water. The phases were separated and the organic layer was dried over anh. Na2SO4. The solids were filtered and the solvent evaporated to give the title compound (1.06 g, 66%) which was used in the next step without further purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([C:12]2[C:20]3[C:19]4[CH:21]=[C:22]([NH2:25])[CH:23]=[CH:24][C:18]=4[O:17][C:16]=3[C:15]([O:26][CH3:27])=[CH:14][CH:13]=2)=[O:11])=[CH:5][CH:4]=1.[C:28](Cl)(=[O:30])[CH3:29].N1C=CC=CC=1>C1COCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([C:12]2[C:20]3[C:19]4[CH:21]=[C:22]([NH:25][C:28](=[O:30])[CH3:29])[CH:23]=[CH:24][C:18]=4[O:17][C:16]=3[C:15]([O:26][CH3:27])=[CH:14][CH:13]=2)=[O:11])=[CH:5][CH:4]=1
Reactant: COc1ccc(NC(=O)c2ccc(OC)c3oc4ccc(N)cc4c23)cc1
Reactant: CC(=O)Cl
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: COc1ccc(NC(=O)c2ccc(OC)c3oc4ccc(NC(C)=O)cc4c23)cc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
N1-(4-methoxyphenyl)-4-methoxy-8-amino-dibenzo[b,d]furan-1-carboxamide (90 mg, 0.248 mmol) (step 2) was treated with acetyl chloride (1.1 eq.) in THF (10 ml) containing pyridine (1.1 eq) at 0° C. and allowed to warm to room temperature. The reaction was stirred at room temperature for 16 h. THF was evaporated and the residue was washed ethanol to obtain 40 mg of N1-(4-methoxyphenyl)-4-methoxy-8-acetamido-dibenzo[b,d]furan-1-carboxamide as white solid; mp: 285° C.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]2[S:21][CH:20]=[CH:19][N:5]2[C:6](=[O:18])[C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=1.[CH:22]1([CH2:25][O:26][C:27]2[CH:28]=[C:29]([CH:32]=[CH:33][C:34]=2[O:35][CH3:36])[CH:30]=O)[CH2:24][CH2:23]1.[O-]CC.[Na+]>C(O)C>[CH:22]1([CH2:25][O:26][C:27]2[CH:28]=[C:29](/[CH:30]=[CH:1]/[C:2]3[N:3]=[C:4]4[S:21][CH:20]=[CH:19][N:5]4[C:6](=[O:18])[C:7]=3[C:8]3[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:15])[F:16])=[CH:10][CH:9]=3)[CH:32]=[CH:33][C:34]=2[O:35][CH3:36])[CH2:23][CH2:24]1
Reactant: COc1ccc(C=O)cc1OCC1CC1
Reactant: Cc1nc2sccn2c(=O)c1-c1ccc(C(F)(F)F)cc1
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: COc1ccc(/C=C/c2nc3sccn3c(=O)c2-c2ccc(C(F)(F)F)cc2)cc1OCC1CC1
Yield: 42.9 %

Procedure:
The title compound was synthesized by condensation of Intermediate 5 (400 mg, 1.350 mmol) with 3-cyclopropylmethoxy-4-methoxybenzaldehyde (417 mg, 2.025 mmol) in presence of sodium ethoxide (183 mg, 2.701 mmol) in ethanol (20 ml) according to the procedure described in Example 24 to give 289 mg of the desired product as an off-white solid; 1H NMR (300 MHz, DMSO-d6) δ 0.23-0.30 (m, 2H), 0.50-0.58 (m, 2H), 1.12-1.18 (m, 1H), 3.72-3.80 (m, 5H), 6.60 (d, J=15.6 Hz, 1H) 6.94-7.00 (m, 3H), 7.48-7.53 (m, 1H), 7.58-7.64 (m, 2H), 7.78-7.84 (m, 3H), 7.98-8.05 (m, 1H); ESI-MS (m/z) 499.12 (M+H)+.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[N:9][N:10]([C:11]3[N:16]=[C:15]([N:17]4[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]4)[CH:14]=[CH:13][CH:12]=3)[C:4]=2[CH:3]=1.C([Sn](CCCC)(CCCC)[C:35]1[S:39][N:38]=[C:37]([CH3:40])[CH:36]=1)CCC>CN(C)C(=O)C>[CH3:40][C:37]1[CH:36]=[C:35]([C:2]2[N:7]=[CH:6][C:5]3[CH:8]=[N:9][N:10]([C:11]4[N:16]=[C:15]([N:17]5[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:27])[CH3:28])=[O:24])[CH2:19][CH2:18]5)[CH:14]=[CH:13][CH:12]=4)[C:4]=3[CH:3]=2)[S:39][N:38]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1cc(C)ns1
Reactant: CC(C)(C)OC(=O)N1CCN(c2cccc(-n3ncc4cnc(Cl)cc43)n2)CC1
Solvent: CC(=O)N(C)C
Product: Cc1cc(-c2cc3c(cn2)cnn3-c2cccc(N3CCN(C(=O)OC(C)(C)C)CC3)n2)sn1
Temperature: 150 °C
Yield: 46.9 %

Procedure:
A solution of tert-butyl 4-[6-(6-chloropyrazolo[4,3-c]pyridin-1-yl)-2-pyridyl]piperazine-1-carboxylate (120 mg, 0.290 mmol) and palladium(0)tetrakis(triphenylphosphine) (34 mg, 0.0290 mmol) in N,N-dimethylacetamide 1.0 mL was added tributyl-(3-methylisothiazol-5-yl)stannane (224 mg, 0.579 mmol). The reaction mixture heated at 150° C. for 45 min in a microwave (Biotage Inc.). The reaction mixture was filtered through celite and concentrated. The crude product was diluted with EtOAc then washed with water. The organic layers was dried with sodium sulfate, filtered, and concentrated in vacuum. The crude product was purified by flash chromatography (EtOAc/Heptane eluted at 20% EtOAc) to give tert-butyl 4-[6-[6-(3-methylisothiazol-5-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]piperazine-1-carboxylate (65 mg) 47% yield:
Reaction SMILES: COCCO[AlH2-]OCCOC.[Na+].[CH:13]1([CH2:16][N:17]([CH2:39][CH2:40][CH3:41])[C:18]([C:20]2[N:24]3[CH2:25][CH2:26][N:27]([C:28]4[C:33]([CH3:34])=[CH:32][C:31]([CH3:35])=[CH:30][C:29]=4[CH3:36])[C:23]3=[N:22][C:21]=2[CH2:37]C)=O)[CH2:15][CH2:14]1.[OH-].[Na+]>C1(C)C=CC=CC=1>[CH:13]1([CH2:16][N:17]([CH2:18][C:20]2[N:24]3[CH2:25][CH2:26][N:27]([C:28]4[C:33]([CH3:34])=[CH:32][C:31]([CH3:35])=[CH:30][C:29]=4[CH3:36])[C:23]3=[N:22][C:21]=2[CH3:37])[CH2:39][CH2:40][CH3:41])[CH2:15][CH2:14]1
Reactant: CCCN(CC1CC1)C(=O)c1c(CC)nc2n1CCN2c1c(C)cc(C)cc1C
Agent: COCCO[AlH2-]OCCOC
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Product: CCCN(Cc1c(C)nc2n1CCN2c1c(C)cc(C)cc1C)CC1CC1
Temperature: 25 °C
Reaction time: 24 h
Yield: 65 %

Procedure:
A solution of Red-Al (3.3 M in toluene, 0.70 mL, 2.33 mmol) was added dropwise to a solution of 2-ethyl-7-(2,4,6-trimethyl-phenyl)-6,7-dihydro-5H-imidazo[1,2-α]imidazole-3-carboxylic acid cyclopropylmethyl-propyl-amide (0.177 g, 0.46 mmol) in toluene (3 mL) at 0° C. After stirring at room temperature for 24 h, the reaction mixture was cooled to 0° C. and I N sodium hydroxide (10 mL) was added dropwise. The above mixture was extracted with dichloromethane (40 mL), and the organic extracts were washed with water and dried over anhydrous sodium sulfate. Solvents were removed in vacuo to afford the title compound as a light yellow oil which solidified upon cooling (109 mg, 65% yield). The purity of the product was determined to be 91% by LC/MS. 1H NMR (CDCl3, 300 MHz) δ 6.85 (s, 2H), 4.09–3.96 (m, 4H), 3.45 (s, 2H), 2.44 (t, J=7.1 Hz, 2H), 2.29 (d, J=6.5 Hz, 2H), 2.23 (s, 3H), 2.19 (s, 6H), 2.04 (s, 3H), 1.46 (quintet, J=7.3 Hz, 2H), 1.28–1.25 (m, 1H), 0.87 (t, J=7.2 Hz, 3H), 0.49–0.46 (m, 2H), 0.09–0.06 (m, 2H); 13C NMR (CDCl3, 75 MHz) δ 155.4, 137.1, 136.9, 136.0, 135.0, 129.7, 117.7, 58.5, 55.5, 53.8, 48.0, 42.4, 20.9, 20.3, 18.2, 13.3, 12.0, 8.9, 4.0. Mass spec.: 367.24 (MH+).
Reaction SMILES: [CH2:1]([C:3]1[N:10]=[C:9]([CH2:11][O:12][Si:13]([CH:20]([CH3:22])[CH3:21])([CH:17]([CH3:19])[CH3:18])[CH:14]([CH3:16])[CH3:15])[CH:8]=[CH:7][C:4]=1[C:5]#[N:6])[CH3:2].[NH2:23][OH:24]>>[CH2:1]([C:3]1[C:4]([C:5](=[N:23][OH:24])[NH2:6])=[CH:7][CH:8]=[C:9]([CH2:11][O:12][Si:13]([CH:14]([CH3:15])[CH3:16])([CH:20]([CH3:21])[CH3:22])[CH:17]([CH3:19])[CH3:18])[N:10]=1)[CH3:2]
Reactant: NO
Reactant: CCc1nc(CO[Si](C(C)C)(C(C)C)C(C)C)ccc1C#N
Product: CCc1nc(CO[Si](C(C)C)(C(C)C)C(C)C)ccc1C(N)=NO

Procedure:
The crude product of the title compound was synthesized by conducting the reaction similar to that mentioned in Example 1 (1d) using 2-ethyl-6-{[(triisopropylsilyl)oxy]methyl}nicotinonitrile (0.75 g, 2.4 mmol) that was obtained in Example 25 (25a) and a 40% aqueous solution of hydroxylamine (0.5 mL). Subsequently, the crude product of the title compound thus obtained was purified by chromatography on a silica gel column using a mixed solvent of ethyl acetate and hexane (3:7 to 1:1) as the eluent to afford the title compound (0.80 g) in a yield of 95% as a white crystalline solid.
Reaction SMILES: [CH2:1]([CH:4]1[CH2:9][CH2:8][CH:7]([CH:10]2[CH2:15][CH2:14][CH:13]([CH:16]=[CH:17][C:18]3[CH:23]=[C:22]([Si](C)(C)C)[C:21]([O:28][CH2:29][CH3:30])=[C:20]([F:31])[C:19]=3[C:32]([F:35])([F:34])[F:33])[CH2:12][CH2:11]2)[CH2:6][CH2:5]1)[CH2:2][CH3:3].O>C1COCC1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1>[CH2:1]([CH:4]1[CH2:5][CH2:6][CH:7]([CH:10]2[CH2:11][CH2:12][CH:13]([CH:16]=[CH:17][C:18]3[CH:23]=[CH:22][C:21]([O:28][CH2:29][CH3:30])=[C:20]([F:31])[C:19]=3[C:32]([F:35])([F:33])[F:34])[CH2:14][CH2:15]2)[CH2:8][CH2:9]1)[CH2:2][CH3:3]
Reactant: CCCC1CCC(C2CCC(C=Cc3cc([Si](C)(C)C)c(OCC)c(F)c3C(F)(F)F)CC2)CC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: O
Product: CCCC1CCC(C2CCC(C=Cc3ccc(OCC)c(F)c3C(F)(F)F)CC2)CC1
Reaction time: 2 h

Procedure:
16.03 g of crude of β-(4-(4-propylcyclohexyl)cyclohexyl)-2-trifluoromethyl-3-fluoro-4-ethoxy-5-trimethylsilyl styrene was dissolved in 35 mL of THF, to which 23.4 mL of tetrabutyl ammonium fluoride/THF solution (1 mol/L) was dropped and stirred for 2 hours. The reaction solution was poured into 100 ml of water and extracted with 200 ml of toluene. The organic layer was washed with 100 ml of an aqueous saturated sodium chloride solution and dried over anhydrous magnesium sulfate. The residue was purified by silica gel column chromatography (eluent: heptane/toluene=8/2) and further recrystallized twice from a heptane/ethanol mixed solvent to obtain 7.89 g of β-(4-(4-propylcyclohexyl)cyclohexyl)-2-trifluoromethyl-3-fluoro-4-ethoxy styrene. The compound showed a liquid crystal phase and the transition points were as shown below.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]([CH2:13][C:14]1[CH:19]=[C:18]([N+:20]([O-])=O)[CH:17]=[CH:16][C:15]=1[CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH3:12])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[NH4+]>CO.C1COCC1.[Zn]>[NH2:20][C:18]1[CH:17]=[CH:16][C:15]([CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])=[C:14]([CH2:13][N:11]([C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:10])[CH3:12])[CH:19]=1
Reactant: CCOC(=O)Cc1ccc([N+](=O)[O-])cc1CN(C)C(=O)OCc1ccccc1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: C1CCOC1
Solvent: CO
Product: CCOC(=O)Cc1ccc(N)cc1CN(C)C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 81.3 %

Procedure:
To a solution of 15B (2.062 g, 5.34 mmol) in methanol (30 mL) and THF (5 mL) was added zinc (dust) (3.49 g, 53.4 mmol) and ammonium chloride (5.71 g, 107 mmol). The resulting solution was stirred at rt for 18 h. MeOH was removed under reduced pressure, to the residue Na2CO3 (aq, 100 mL) and EtOAc (250 mL) were added, and the suspension was stirred vigorously for 10 min, filtered though glass frit, solid residue was washed with EtOAc (3×150 mL). Combined EtOAc fractions were washed with std. Na2CO3 (aq, 2×100 mL), water (2×100 mL), brine (1×100 mL) and dried (Na2SO4). EtOAc was removed under reduced pressure and the residue was purified by flash chromatography (0-100% EtOAc/hexanes). Fractions were combined and concentrated under reduced pressure to give 15C (1.546 g, 4.34 mmol, 81% yield) as an amber oil. MS (ESI) m/z: 357.2 [M+1]+. 1H NMR: (400 MHz, CDCl3) δ ppm 7.28-7.47 (5H, m), 7.00 (1H, d, J=7.28 Hz), 6.56 (1H, d, J=8.03 Hz), 6.38-6.52 (1H, m), 5.13-5.22 (2H, m), 4.48 (2H, br. s.), 4.08 (2H, br. s.), 3.44-3.58 (2H, m), 2.85 (3H, d, J=17.82 Hz), 1.21 (3H, d, J=7.03 Hz).
Reaction SMILES: [C:1]1([C:7]2[C:18]3[CH:17]=[C:16]4[C:12]([CH2:13][CH2:14][CH2:15]4)=[CH:11][C:10]=3[CH2:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li][Li].[Si:21]([CH3:25])([CH3:24])(Cl)[Cl:22]>C1COCC1>[Cl:22][Si:21]([CH3:25])([CH3:24])[CH:9]1[C:10]2[C:18](=[CH:17][C:16]3[CH2:15][CH2:14][CH2:13][C:12]=3[CH:11]=2)[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:8]1
Reactant: C1=C(c2ccccc2)c2cc3c(cc2C1)CCC3
Reactant: C[Si](C)(Cl)Cl
Agent: [Li][Li]
Solvent: C1CCOC1
Product: C[Si](C)(Cl)C1C=C(c2ccccc2)c2cc3c(cc21)CCC3
Temperature: 25 °C
Reaction time: 8 h
Yield: 91.1 %

Procedure:
1,2,3,5-Tetrahydro-7-phenyl-s-indacene, dilithium salt (12.2075 g, 0.05102 moles) in THF (50 mL) was added dropwise to a solution of Me2SiCl2 (19.5010 g, 0.1511 moles) in THF (100 mL) at 0° C. This mixture was then allowed to stir at room temperature overnight. After the reaction period the volatiles were removed and the residue extracted and filtered using hexane. The removal of the hexane resulted in the isolation of the desired product as a yellow oil (15.1492 g, 91.1% yield). 1H NMR (CDCl3): d0.33 (s, 3 H), 0.38 (s, 3 H), 2.20 (p, 3JHH=7.5 Hz, 2 H), 2.9-3.1 (m, 4 H), 3.84 (s, 1 H), 6.69 (d, 3JHH=2.8 Hz, 1 H), 7.3-7.6 (m, 7 H), 7.68 (d, 3JHH=7.4 Hz, 2 H). 13C NMR (CDCl3): d0.24, 0.38, 26.28, 33.05, 33.18, 46.13, 116.42, 119.71, 127.51, 128.33, 128.64, 129.56, 136.51, 141.31, 141.86, 142.17, 142.41, 144.62. GC-MS: Calculated for C20H21ClSi 324.11, found 324.05.