Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([OH:13])(=O)[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[Cl:47][C:48]1[CH:53]=[CH:52][C:51]([C:54]2[N:59]=[C:58]([NH:60][CH2:61][CH2:62][NH:63][C:64](=[O:66])[CH3:65])[CH:57]=[C:56]([N:67]3[CH2:72][CH2:71][NH:70][CH2:69][CH2:68]3)[N:55]=2)=[CH:50][CH:49]=1>CN1C(=O)CCC1>[Cl:47][C:48]1[CH:49]=[CH:50][C:51]([C:54]2[N:59]=[C:58]([NH:60][CH2:61][CH2:62][NH:63][C:64](=[O:66])[CH3:65])[CH:57]=[C:56]([N:67]3[CH2:72][CH2:71][N:70]([C:1]([C:2]4[CH:11]=[CH:10][C:9]5[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=5)[N:3]=4)=[O:13])[CH2:69][CH2:68]3)[N:55]=2)=[CH:52][CH:53]=1
Reactant: O=C(O)c1ccc2ccccc2n1
Reactant: CC(=O)NCCNc1cc(N2CCNCC2)nc(-c2ccc(Cl)cc2)n1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN1CCCC1=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(=O)NCCNc1cc(N2CCN(C(=O)c3ccc4ccccc4n3)CC2)nc(-c2ccc(Cl)cc2)n1
Reaction time: 12 h

Procedure:
A solution of quinaldic acid (60 μl of a 0.3M solution in NMP), HATU (60 μl of a 0.3M solution in NMP) and diisopropylethylamine (60 μl of a 0.3M solution in NMP) was shaken at ambient temperature in a well of a 96 position microtitre plate for 5 min. N-(2-{[2-(4-chlorophenyl)-6-piperazin-1-ylpyrimidin-4-yl]amino}ethyl)acetamide (30 μl of a 0.3M solution in NMP) was then added and the mixture shaken for a further 12 hr. Purification via ion exchange silica (SCX) yields the title compound.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][NH:8][C:9](=[O:23])[C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17](=O)[CH3:18])=[C:12]([N+:20]([O-])=O)[CH:11]=1.C(O)(=O)C>[Pd].C(O)C>[CH3:18][C:17]1[NH:20][C:12]2[CH:11]=[C:10]([C:9](=[O:23])[NH:8][CH2:7][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)[CH:15]=[CH:14][C:13]=2[N:16]=1
Reactant: CC(=O)Nc1ccc(C(=O)NCc2ccccn2)cc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCO
Solvent: CC(=O)O
Product: Cc1nc2ccc(C(=O)NCc3ccccn3)cc2[nH]1
Temperature: 80 °C
Reaction time: 7 h
Yield: 67.3 %

Procedure:
5% palladium/carbon (0.10 g) is added to a mixture of preliminarily purified N-(pyridylmethyl)-4-acetylamino-3-nitrobenzamide (1.00 g), acetic acid (8 ml), and ethanol (12 ml), and then solution is stirred for seven hours at 80° C. under a nitrogen environment. The solids are separated through filtration and the filtrate is then concentrated. Ethyl acetate is added to the residue and crystals are formed. The crystals are separated through filtration, then dried and thus, 2-methyl-5-[(2-pyridylmethyl) carbamoyl]benzimidazole (0.57 g) is obtained. 1H-NMR (CDCl3, δ): 2.52 (3H, s), 4.59 (2H, d, J=5.9 Hz), 7.26 (1H, dd, J=7.1 and 5.1 Hz), 7.33 (1H, d, J=7.8 Hz), 7.50 (1H, d, J=8.4 Hz), 7.72-7.78 (2H, m), 8.08(1H, s), 8.51 (1H, d, J=4.8 Hz), 9.04 (1H, t, J=5.8 Hz), 12.44 (1H, s).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[N:3][C:2]=1[C:7]1[C:8]([Cl:16])=[CH:9][C:10]([Cl:15])=[C:11]([CH2:13][OH:14])[CH:12]=1.O1C[CH2:20][CH2:19][CH2:18]1.[H-].[Na+].C(Br)C=C>O>[CH2:20]([O:14][CH2:13][C:11]1[CH:12]=[C:7]([C:2]2[N:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[C:8]([Cl:16])=[CH:9][C:10]=1[Cl:15])[CH:19]=[CH2:18]
Reactant: OCc1cc(-c2ncccn2)c(Cl)cc1Cl
Reactant: C1CCOC1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C=CCBr
Product: C=CCOCc1cc(-c2ncccn2)c(Cl)cc1Cl
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To a 250 ml single neck round bottom flask equipped with a reflux condensor and an argon inlet was added 5.10 gm of the 5-pyrimidyl-2,4-dichlorophenylcarbinol and 100 of anhydrous tetrahydrofuran. The system was cooled to 0° C. and after cooling 0.53 gm sodium hydride added. The system was stirred for 20 additional minutes and 2.1 ml of allyl bromide was then added. The system was allowed to come to room temperature over 1/2-hour and stirred there for an additional 2 hours. Afterwards the system was heated at reflux for 17 hours. At this time, water was added to the system and the product extracted with methylene chloride. The methylene chloride was then washed with water and then dried over sodium sulfate. The methylene chloride was removed by stripping to give 5.47 gm of the 5-pyrimidyl-2,4-dichlorophenylcarbinol allylether as an orange liquid and listed as Compound No. 2, Table I.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][CH2:11][C@H:10]([C:15](O)=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:18]2[CH:23]=[CH:22][C:21]([C:24]#[N:25])=[C:20]([F:26])[CH:19]=2)[N:3]=1.CN(C(ON1N=N[C:37]2[CH:38]=[CH:39][CH:40]=[N:41][C:36]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C1(N)CCCC1>CN(C=O)C.O>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][CH2:11][C@H:10]([C:15]([NH:41][CH:36]3[CH2:37][CH2:38][CH2:39][CH2:40]3)=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:18]2[CH:23]=[CH:22][C:21]([C:24]#[N:25])=[C:20]([F:26])[CH:19]=2)[N:3]=1
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Reactant: C[C@@H]1CC[C@H](C(=O)O)CN1c1cc(-c2ccc(C#N)c(F)c2)nc(N)n1
Agent: F[P-](F)(F)(F)(F)F
Agent: NC1CCCC1
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: C[C@@H]1CC[C@H](C(=O)NC2CCCC2)CN1c1cc(-c2ccc(C#N)c(F)c2)nc(N)n1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 86.2 %

Procedure:
To a solution of (3S,6R)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-6-methyl-3-piperidinecarboxylic acid (170 mg, 0.478 mmol) and HATU (218 mg, 0.574 mmol) in DMF (3 mL) was added Hunig's base (0.167 mL, 0.957 mmol), and the mixture was stirred at room temperature for 5 minutes. Then, cyclopentylamine (44.8 mg, 0.526 mmol) was added, and the reaction mixture was stirred at room temperature for 0.5 hours. LCMS showed reaction was completed. The reaction was poured into water, and the formed solid was filtered, washed by water and dried to afford the title compound (174 mg) as a yellow solid. LC-MS (ES) m/z=423 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1([CH3:28])[CH2:7][CH:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][CH:23]([OH:25])[CH3:24])=[CH:17][CH:16]=3)[CH:12]=[CH:11][N:10]=2)[CH2:5][C:4]([CH3:27])([CH3:26])[NH:3]1.[C:29]1([CH3:39])[CH:34]=[CH:33][C:32]([S:35](Cl)(=[O:37])=[O:36])=[CH:31][CH:30]=1>N1C=CC=CC=1>[CH3:24][CH:23]([O:25][S:35]([C:32]1[CH:33]=[CH:34][C:29]([CH3:39])=[CH:30][CH:31]=1)(=[O:37])=[O:36])[CH2:22][CH2:21][C:18]1[CH:19]=[CH:20][C:15]([C:13]2[CH:12]=[CH:11][N:10]=[C:9]([NH:8][CH:6]3[CH2:5][C:4]([CH3:27])([CH3:26])[NH:3][C:2]([CH3:1])([CH3:28])[CH2:7]3)[N:14]=2)=[CH:16][CH:17]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: CC(O)CCc1ccc(-c2ccnc(NC3CC(C)(C)NC(C)(C)C3)n2)cc1
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OC(C)CCc2ccc(-c3ccnc(NC4CC(C)(C)NC(C)(C)C4)n3)cc2)cc1

Procedure:
The title compound was prepared from 4-{4-[2-(2,2,6,6-tetramethyl-piperidin-4-ylamino)-pyrimidin-4-yl]-phenyl}-butan-2-ol and p-toluenesulfonyl chloride in pyridine. Yield: 182 mg (93%).
Reaction SMILES: [CH2:1]([NH:3][CH2:4][CH3:5])[CH3:2].Cl[Si:7]([CH3:14])([CH3:13])[O:8][Si:9](Cl)([CH3:11])[CH3:10]>CCOCC>[CH2:1]([N:3]([Si:7]([CH3:14])([CH3:13])[O:8][Si:9]([N:3]([CH2:4][CH3:5])[CH2:1][CH3:2])([CH3:11])[CH3:10])[CH2:4][CH3:5])[CH3:2]
Reactant: C[Si](C)(Cl)O[Si](C)(C)Cl
Reactant: CCNCC
Solvent: CCOCC
Product: CCN(CC)[Si](C)(C)O[Si](C)(C)N(CC)CC
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Diethylamine, 184 g. (2.50 mole) of 400 ml. of anhydrous ether were added to a one-liter multi-necked round bottom flask equipped with reflux condenser, pressure equalizing addition funnel, thermometer and stirrer, which was maintained under a positive pressure of argon. The solution was chilled with an ice water bath to 5°-10° C. during the dropwise addition of 100 g. (0.50 mole) of 1,3-dichloro-1,1,3,3,-tetramethyldisiloxane. After addition was completed the mixture was stirred overnight at room temperature (20°-25° C.). The mixture was then filtered and the filtrate was concentrated by rotary evaporation. The resulting residue was distilled at reduced pressure and yielded 81 g. (0.29 mole; 60% theoretical) of V (b.p. 75°-80° C., 2 mm. Hg.).
Reaction SMILES: Br[C:2]([C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[C:6]([O:12][CH3:13])[CH:5]=1)=[CH2:3].[Li]C(C)(C)C.[CH:19]([CH:21]=[CH2:22])=[O:20]>>[CH3:13][O:12][C:6]1[CH:5]=[C:4]([CH:2]=[CH:3][CH:19]([OH:20])[CH:21]=[CH2:22])[CH:9]=[CH:8][C:7]=1[O:10][CH3:11]
Reactant: C=C(Br)c1ccc(OC)c(OC)c1
Reactant: C=CC=O
Agent: [Li]C(C)(C)C
Product: C=CC(O)C=Cc1ccc(OC)c(OC)c1
Yield: 42.3 %

Procedure:
According to the General Procedure C, 1-Bromo-1-(3,4-dimethoxyphenyl)ethene (1.00 g, 4.11 mmol), t-BuLi (6.05 ml, 10.28 mmol) and acrolein (691 mg, 12.33 mmol) are converted to give after workup and chromatography (SiO2, PE/EE=2:1, Rf=0.25) the title compound (382 mg, 1.74 mmol, 42%) as a yellow oil; C13H16O3 (220.26).
Reaction SMILES: [OH:1][CH:2](CO)[CH2:3][C:4]1([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:8][C:7](=[O:9])[N:6]([C:10]2[C:15]([CH3:16])=[CH:14][CH:13]=[CH:12][C:11]=2[CH3:17])[CH2:5]1.O.CO>C1COCC1.C(OCC)(=O)C>[CH3:16][C:15]1[CH:14]=[CH:13][CH:12]=[C:11]([CH3:17])[C:10]=1[N:6]1[C:7](=[O:9])[CH2:8][C:4]([CH2:3][CH:2]=[O:1])([C:18]([O:20][C:21]([CH3:23])([CH3:24])[CH3:22])=[O:19])[CH2:5]1
Reactant: Cc1cccc(C)c1N1CC(CC(O)CO)(C(=O)OC(C)(C)C)CC1=O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: O
Product: Cc1cccc(C)c1N1CC(CC=O)(C(=O)OC(C)(C)C)CC1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 89.6 %

Procedure:
A solution of tert-butyl 3-(2,3-dihydroxypropyl)-1-(2,6-dimethylphenyl)-5-oxopyrrolidine-3-carboxylate (1.2 g, 3.3 mmol) dissolved in THF (8 mL) was treated with NaIO4 (1.4 g, 6.6 mmol) and water (2 mL). After stirring overnight at room temperature, methanol (2 mL) was added and the mixture was diluted with ethyl acetate (15 mL) and washed with water. The aqueous phase was washed with ethyl acetate and the organic layers were combined, dried and the solvent evaporated. The residue was purified by flash chromatography (SiO2, 10-100% EtOAc/hexanes) to yield tert-butyl 1-(2,6-dimethylphenyl)-5-oxo-3-(2-oxoethyl)pyrrolidine-3-carboxylate (980 mg, 88% yield). LC-MS Rt (retention time): 2.28 min, MS: (ES) m/z 332 (M+H+).
Reaction SMILES: [C:1]([OH:11])(=[O:10])[C@H:2]([CH:4]1[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1)[OH:3].[OH-].[K+].C(Cl)(Cl)Cl.[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>[N+](CCCC)(CCCC)(CCCC)CCCC.[I-].C(Cl)Cl>[OH:3][C@@H:2]([CH:4]1[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1)[C:1]([O:11][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:10]
Reactant: BrCc1ccccc1
Reactant: O=C(O)[C@@H](O)C1CCCCC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [I-]
Agent: [K+]
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Product: O=C(OCc1ccccc1)[C@@H](O)C1CCCCC1

Procedure:
A flask was charged with (S)-hexahydromandelic acid (0.88 g, 5.56 mmol), Bu4NI (0.4 g, 1.1 mmol) and KOH (11.1 mL, 5.56 mmol, 0.5 M in water). 11 mL of chloroform was added followed by benzyl bromide (0.66 mL, 5.56 mmol). The mixture was refluxed for 5 h then cooled and diluted with 100 ml CH2Cl2. The layers were separated and the organic was dried and concentrated. Flash Chromatography (7/1 hexane/EtOAc) gave the desired product. RF: 0.37 (4:1 v/v hexanes/EtOAc); 1H NMR (300 MHz, CDCl3) δ1.11-1.38 (m, 11H), 2.65 (d, J=6.3 Hz, 1H), 4.06 (dd, J=6.3, 3.5 Hz, 1H), 5.22 (s, 2H), 7.30-7.39 (m, 5H).
Reaction SMILES: C([O:3][C:4]([C:6]1([CH2:9][CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[CH2:8][O:7]1)=[O:5])C.[OH-].[Na+:23].O>O1CCCC1>[F:21][C:18]([F:19])([F:20])[C:14]1[CH:13]=[C:12]([CH2:11][CH2:10][CH2:9][C:6]2([C:4]([O-:5])=[O:3])[CH2:8][O:7]2)[CH:17]=[CH:16][CH:15]=1.[Na+:23]
Reactant: CCOC(=O)C1(CCCc2cccc(C(F)(F)F)c2)CO1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: O=C([O-])C1(CCCc2cccc(C(F)(F)F)c2)CO1

Procedure:
A solution of 28 g of 2-[3-(3-trifluoromethylphenyl)propyl]oxirane-2-carboxylic acid ethyl ester in 50 ml of tetrahydrofuran is added dropwise to a solution of 92.6 ml of 1 N sodium hydroxide solution and 50 ml of tetrahydrofuran at room temperature. After a clear solution has formed, the solution is concentrated to a viscous mass in vacuo. The mass is dissolved in 70 ml of tetrahydrofuran, the small amount of undissolved material is filtered off, and 200 ml of methylene chloride are added dropwise to the clear filtrate. The voluminous precipitate is filtered off and stirred again with 200 ml of diethyl ether, the mixture is filtered and the solid product is dried over calcium chloride. The title compound of m.p. 64° to 70° C., which contains 2 mols of water of crystallization, is converted into the form containing no water of crystallization, of m.p. >170° C., when dried over phosphorus pentoxide in vacuo (yield: 22.8 g).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH2:10]O)[CH:5]=[N:6][CH:7]=1.S(Cl)([Cl:14])=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH2:10][Cl:14])[CH:5]=[N:6][CH:7]=1
Reactant: O=S(Cl)Cl
Reactant: OCC=Cc1cncc(Br)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: ClCC=Cc1cncc(Br)c1
Yield: 76 %

Procedure:
A solution of 3-(5-bromo-3-pyridinyl)prop-2-en-1-ol (0.85 gms, 3.97 mmol) is diluted with methylene chloride (20 mls). Thionyl chloride (0.27 mls, 97%, leq) is added at room temperature. After one hour a second equivalent of thionyl chloride is added. The reaction is neutralized with saturated aqueous NaHCO3 after an additional hour and extracted with methylene chloride. The organic layer is dried over Na2SO4 and evaporated to yield 0.70 gms of an oil (76%). 1H NMR (CDCl3, 300 MHz) δ8.90 (s, 1H), 8.70 (s, 1H), 8.40 (s, 1H), 6.70 (m, 2H), and 4.30 (d, J=3.8 Hz, 2H).
Reaction SMILES: [CH3:1][C:2]1([CH3:20])[CH2:7][O:6][CH:5]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([CH:18]=[O:19])=[CH:10][CH:9]=2)[O:4][CH2:3]1.CCOCC.[Mg+2].[Br-].[Br-].[CH2:29]([Mg]Cl)[CH:30]([CH3:32])[CH3:31]>C(OCC)C.CO.O.Cl>[CH3:1][C:2]1([CH3:20])[CH2:3][O:4][CH:5]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([CH:18]([OH:19])[CH2:29][CH:30]([CH3:32])[CH3:31])=[CH:10][CH:9]=2)[O:6][CH2:7]1
Reactant: CC1(C)COC(c2ccc(C=O)c3ccccc23)OC1
Reactant: CC(C)C[Mg]Cl
Agent: Cl
Agent: [Br-]
Agent: [Mg+2]
Solvent: CCOCC
Solvent: O
Solvent: CO
Product: CC(C)CC(O)c1ccc(C2OCC(C)(C)CO2)c2ccccc12
Temperature: 25 °C
Reaction time: 16 h
Yield: 36 %

Procedure:
4-(5,5-dimethyl-1,3-dioxan-2-yl)-1-naphthaldehyde (4.0 g, 14.8 mmol) was dissolved in diethyl ether (80 mL). Magnesium bromide diethyl etherate (2.8 g, 10.8 mol) was added followed by a 2M solution of isobutyl magnesium chloride in diethyl ether (8.0 mL, 16 mmol). The mixture was stirred at room temperature for 16 hours, diluted with methanol (1 mL), water (1 mL), and 1 N HCl (20 mL). The phases were separated, and the aqueous phase was extracted with ether (3×50 mL). The combined organic extracts were dried (MgSO4), and concentrated. Flash chromatography of the residue provided the 1.76 g (36%) desired product.
Reaction SMILES: [CH:1](/[C:4]1[C:14]2[O:13][CH2:12][CH2:11][N:10](C(OC(C)(C)C)=O)[CH2:9][C:8]=2[CH:7]=[CH:6][CH:5]=1)=[CH:2]/[CH3:3].C(OCC)(=O)C.[ClH:28]>C(OCC)(=O)C>[ClH:28].[CH:1](/[C:4]1[C:14]2[O:13][CH2:12][CH2:11][NH:10][CH2:9][C:8]=2[CH:7]=[CH:6][CH:5]=1)=[CH:2]/[CH3:3]
Reactant: C/C=C\c1cccc2c1OCCN(C(=O)OC(C)(C)C)C2
Agent: Cl
Solvent: CCOC(C)=O
Product: C/C=C\c1cccc2c1OCCNC2
Temperature: 25 °C
Reaction time: 1 h
Yield: 90.9 %

Procedure:
A mixture of tert-butyl 9-[(1Z)-propa-1-ene-1-yl]-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (170 mg, 0.587 mmol), ethyl acetate (1 ml) and 4N hydrogen chloride-ethyl acetate solution (2 ml) was stirred at room temperature for 1 hr, and the solvent was evaporated under reduced pressure. The residue was recrystallized from a mixed solvent of methanol and ether to give the desired product (120 mg, 90.9%) as a solid.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17](C)(C)[O:18][SiH2]C(C)(C)C)=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:26]1[C:27]2[S:40][CH:39]=[CH:38][C:28]=2[N:29]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[N:30]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH2:17][OH:18])=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:26]1[C:27]2[S:40][CH:39]=[CH:38][C:28]=2[N:29]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[N:30]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)n1nc(-c2cc3cc(C(C)(C)O[SiH2]C(C)(C)C)ccc3n2C(=O)OC(C)(C)C)c2sccc21
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)n1nc(-c2cc3cc(CO)ccc3n2C(=O)OC(C)(C)C)c2sccc21
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 86 %

Procedure:
A solution of 2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-5-(tert-butyl-dimethyl-silanyloxymethyl)-indole-1-carboxylic acid tert-butyl ester [3.8 g, 6.51 mmol, Intermediate (9)]) in anhydrous tetrahydrofuran (40 mL) is cooled to 0° C. To it is added tetrabutylammonium fluoride (1M in tetrahydrofuran, 10 mL) drop wise. Stirred at 0° C. for 20 minutes then at room temperature for 20 minutes. Water (20 mL) is added and extracted three times with ethyl acetate (30 mL). The combined ethyl acetate phases are washed with brine and dried over sodium sulfate. The residue is chromatographed on 35 g silica gel (10-50% ethyl acetate in heptane) to give 2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-5-hydroxymethyl-indole-1-carboxylic acid tert-butyl ester [2.63 g, 85%, Intermediate (10)] as white solid; 1H NMR [(CD3)2SO)]: δ 8.05 (2H, m), 7.62 (1H, s), 7.38 (2H, m), 7.02 (1H, s), 5.21 (1H, t), 4.6 (2H, d), 1.64 (9H, s), 1.25 (9H, s); LC/MS: 470 (M+H).
Reaction SMILES: [CH2:1]([O:4][C@@H:5]1[CH2:10][O:9][C:8]([CH3:12])([CH3:11])[O:7][C@H:6]1[CH:13]=[CH2:14])C=C>C(Cl)Cl>[CH3:12][C:8]1([CH3:11])[O:7][C@@H:6]2[CH:13]=[CH:14][CH2:1][O:4][C@H:5]2[CH2:10][O:9]1
Reactant: C=CCO[C@@H]1COC(C)(C)O[C@H]1C=C
Solvent: ClCCl
Product: CC1(C)OC[C@@H]2OCC=C[C@H]2O1
Temperature: 25 °C

Procedure:
To a solution of trans-5-allyloxy-2,2-dimethyl-4-vinyl-[1,3]dioxane (300 mg, 1.52 mmol) in dry CH2Cl2 (10 mL) was added bis-(tricyclohexylphosphine)benzylidine ruthenium (IV) chloride (125 mg, 0.15 mmol). The mixture was stirred at ambient temperature for ca. 8H, filtered through filter paper and concentrated in vacuo to 1 mL. The residue was purified by flash chromatography with 5% EtOAc-hexane
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][CH2:6][C:7](=O)[CH:8]2[CH2:13][C:14]([O:16]CC)=O.[C:20]1([CH2:26][CH2:27][CH2:28][NH2:29])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.O>C1(C)C=CC=CC=1>[CH:20]1([CH2:26][CH2:27][CH2:28][N:29]2[C@@H:7]3[C@@H:8]([C:9]4[CH:10]=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[C:4]=4[CH2:5][CH2:6]3)[CH2:13][C:14]2=[O:16])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1
Reactant: CCOC(=O)CC1C(=O)CCc2c(OC)cccc21
Reactant: NCCCc1ccccc1
Solvent: Cc1ccccc1
Solvent: O
Product: COc1cccc2c1CC[C@H]1[C@@H]2CC(=O)N1CCCC1CCCCC1
Reaction time: 10 h
Yield: 60.1 %

Procedure:
4.0 g (0.01525 mol) of ethyl 1,2,3,4-tetrahydro-5-methoxy-2-oxo-1-naphthylacetate were dissolved in 80 ml of toluene, 2.29 ml (0.016 mol) of 3-phenylpropylamine were added thereto and the mixture was boiled for 20 hours on a water separator. After concentration the residue was hydrogenated with 1.5 g of Raney-nickel in 150 ml of ethanol at 120° and 140 bar for 10 hours. The product was chromatographed over silica gel with cyclohexane/ethyl acetate 2:1. There were obtained 3.13 g (61%) of oily rac-cis-3-(3-cyclohexyl-propyl)-1,3,3a,4,5,9b-hexahydro-6-methoxy-2H-benzo[e]indol-2-one.
Reaction SMILES: C[O:2][C:3](=[O:30])[C:4]([CH3:29])([S:6][C:7]1[S:8][CH:9]=[C:10]([CH2:12][CH2:13][O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]#[C:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:17][CH:16]=2)[N:11]=1)[CH3:5].[OH-].[Na+]>CO.O1CCCC1>[CH3:29][C:4]([S:6][C:7]1[S:8][CH:9]=[C:10]([CH2:12][CH2:13][O:14][C:15]2[CH:16]=[CH:17][C:18]([C:21]#[C:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:19][CH:20]=2)[N:11]=1)([CH3:5])[C:3]([OH:30])=[O:2]
Reactant: COC(=O)C(C)(C)Sc1nc(CCOc2ccc(C#Cc3ccccc3)cc2)cs1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)(Sc1nc(CCOc2ccc(C#Cc3ccccc3)cc2)cs1)C(=O)O
Temperature: 25 °C
Reaction time: 4 h
Yield: 74.9 %

Procedure:
2-Methyl-2-[(4-{2-[4-(phenylethynyl)phenoxy]ethyl}-1,3-thiazol-2-yl)thio]propionic acid methyl ester (400 mg) obtained in Example 144-3 was dissolved in methanol (4 mL) and tetrahydrofuran (4 mL), aqueous sodium hydroxide solution (1 mol/L, 2 mL) was added, and the mixture was stirred at room temperature for 4 hr. The reaction mixture was concentrated under reduced pressure, aqueous 10% citric acid solution was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=1:1 to 0:1) to give the title compound (290 mg) as a slightly yellow oil.
Reaction SMILES: [CH:1]1([C:6]2[CH:13]=[CH:12][C:9]([CH:10]=[O:11])=[C:8]([OH:14])[CH:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.IC.[C:17](=O)([O-])[O-].[K+].[K+].Cl>CN(C)C=O.O.C(OCC)(=O)C>[CH:1]1([C:6]2[CH:13]=[CH:12][C:9]([CH:10]=[O:11])=[C:8]([O:14][CH3:17])[CH:7]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: O=Cc1ccc(C2CCCC2)cc1O
Reactant: O=C([O-])[O-]
Agent: Cl
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: O
Product: COc1cc(C2CCCC2)ccc1C=O
Temperature: 75 °C
Reaction time: 2 h
Yield: 94 %

Procedure:
0.770 g of 4-cyclopentyl-2-hydroxybenzaldehyde, 0.38 mL of iodomethane, and 0.839 g of potassium carbonate were suspended in 7.7 mL of N,N-dimethylformamide, and this mixture was stirred for 2 hours at 75° C. The reaction mixture, which was cooled to room temperature, was added to a mixture of ethyl acetate and water, and then adjusted to pH 3 with 6M hydrochloric acid, and the organic phase was separated therefrom. After the resultant organic phase was washed with water and a saturated sodium chloride solution successively, the washed phase was dried over anhydrous magnesium sulfate, and the solvent was distilled out under reduced pressure to yield 0.777 g of 4-cyclopentyl-2-methoxybenzaldehyde as yellow oil.