Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][C:10](=[O:17])[CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(NC1(C(O)=O)CC1)(O[C:21](C)(C)[CH3:22])=O>>[C:1]([O:5][C:6]([NH:8][C:9]1([C:10](=[O:17])[CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:22][CH2:21]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]
Reactant: CC(C)(C)OC(=O)NC1(C(=O)O)CC1
Reactant: CCOC(=O)CC(=O)CNC(=O)OC(C)(C)C
Product: CCOC(=O)CC(=O)C1(NC(=O)OC(C)(C)C)CC1

Procedure:
A tautomeric mixture of ethyl 3-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-3-oxopropanoate and (Z)-ethyl 3-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-3-hydroxyacrylate (3.15 g, 11.61 mmol, 90% yield) as an off white solid was prepared according the procedures described for Intermediate 601, using 1-(Boc-amino)cyclopropanecarboxylic acid (Chem-Impex International, Inc., cat #04052) (2.59 g, 12.87 mmol) as the reagent. m/z (ESI, +ve) 294.2 (M+23)+.
Reaction SMILES: [CH2:1]([C:4]#[C:5][SiH:6]([CH:10]([CH3:12])[CH3:11])[CH:7]([CH3:9])[CH3:8])[CH:2]=[CH2:3].[CH2:13]([Mg]Br)C=C>>[CH2:13]=[C:1]([C:4]#[C:5][SiH:6]([CH:10]([CH3:12])[CH3:11])[CH:7]([CH3:8])[CH3:9])[CH2:2][CH3:3]
Reactant: C=CC[Mg]Br
Reactant: C=CCC#C[SiH](C(C)C)C(C)C
Product: C=C(C#C[SiH](C(C)C)C(C)C)CC

Procedure:
This material was synthesized by methods identical to those used to prepare allyldiisopropylsilyl acetylene (Example 1), simply substituting 2-lithio-1-butene (generated in situ by treating 2-bromo-1-butene with n-BuLi in tetrahydrofuran at −78° C.) for allyl magnesium bromide. 1H-NMR (200 MHz, CDCl3) δ=5.76 (q, J=1.2 Hz, 1H), 5.55 (quint, J=1.2 Hz, 1H), 2.41 (s, 1H), 1.06 (br. s, 14H), 2.19 (q, t, J=9.5, 1.2 Hz, 2H), 1.10 (t, J=9 Hz, 3H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[CH2:4][C:5]1[C:6]([CH3:11])=[N:7][NH:8][C:9]=1[CH3:10].[Br:13][C:14]1[CH:21]=[CH:20][C:17]([CH2:18]Br)=[CH:16][CH:15]=1.C([O-])([O-])=O.[K+].[K+]>C(#N)C>[CH3:1][O:2][C:3](=[O:12])[CH2:4][C:5]1[C:9]([CH3:10])=[N:8][N:7]([CH2:18][C:17]2[CH:20]=[CH:21][C:14]([Br:13])=[CH:15][CH:16]=2)[C:6]=1[CH3:11]
Reactant: BrCc1ccc(Br)cc1
Reactant: COC(=O)Cc1c(C)n[nH]c1C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COC(=O)Cc1c(C)nn(Cc2ccc(Br)cc2)c1C
Temperature: 50 °C
Reaction time: 12 h

Procedure:
To a solution of (3,5-dimethyl-1H-pyrazol-4-yl)-acetic acid methyl ester (6 g, 36 mmol) and 4-bromobenzyl bromide (8.9 g, 36 mmol) in 80 ml acetonitrile was added K2CO3 (4.9 g, 36 mmol). The mixture was stirred for 12 h at room temperature, 12 h at 50° C., and after addition of an additional 1 g of K2CO3 the mixture was stirred for another 12 h at room temperature. The mixture was concentrated by under reduced pressure, poured into water and extracted twice with ethyl acetate, dried with MgSO4 and evaporated under reduced pressure.
Reaction SMILES: [CH3:1][C:2]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:3]=1[O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12](=[N:16][O:17][CH3:18])[C:13](O)=[O:14].CN(C)C=O.S(Cl)([Cl:31])=O>C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:3]=1[O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12](=[N:16][O:17][CH3:18])[C:13]([Cl:31])=[O:14]
Reactant: CON=C(C(=O)O)c1ccccc1COc1cc(C)ccc1C
Reactant: O=S(Cl)Cl
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Product: CON=C(C(=O)Cl)c1ccccc1COc1cc(C)ccc1C
Temperature: 60 °C
Reaction time: 5 h

Procedure:
2-[2-(2,5-Dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetic acid (9.40 g, 30 mmol, E/Z=20/80) was dissolved in dimethylformamide (DMF)(0.11 g, 1.5 mmol) and toluene (20 ml). A solution of 95% thionyl chloride (4.13 g, 33 mmol) and toluene (10 ml) was added dropwise at 60° C. over 5 hours. The mixture was stirred at 60° C. for 5 hours. After completion of the reaction, the mixture was concentrated under reduced pressure to a total amount of 30 g to give crude 2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetyl chloride.
Reaction SMILES: [CH:1]([C:3]1[CH2:4][CH2:5][CH2:6][O:7][CH:8]=1)=[CH2:2].[CH:9]([CH:11]=[CH2:12])=[O:10].O>C(Cl)Cl>[O:7]1[C@H:8]2[C:3](=[CH:1][CH2:2][CH2:12][C@H:11]2[CH:9]=[O:10])[CH2:4][CH2:5][CH2:6]1
Reactant: C=CC1=COCCC1
Reactant: C=CC=O
Solvent: ClCCl
Solvent: O
Product: O=C[C@@H]1CCC=C2CCCO[C@@H]21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 2.613 g 5-ethenyl-3,4-dihydro-2H-pyran and 8.9 mL acrolein (90% pure) was dissolved in 39 mL CH2Cl2 and stirred overnight at RT. The reaction was added to water and extracted with CH2Cl2. The crude extract was filtered, concentrated using a rotovap, then purified on silica gel to provide the title compound. 1H NMR (500 MHz, CDCl3) δ=1.64-1.98 (m, 5H), 2.04-2.16 (m, 1H), 2.23-2.29 (m, 1H), 2.34-2.38 (m, 1H), 2.60-2.64 (m, 1H), 3.55-3.61 in, 1H), 3.99-4.04 (m, 1H), 4.21 (d, J=5.6 Hz, 1H), 5.55 (s, 1H), 9.88 (s, 1H) ppm.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([O:12][CH3:13])=[O:11])=[CH:4][CH:3]=1.[C@H:14]1(O)[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:16][CH2:15]1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC>O1CCCC1.O>[C@@H:14]1([O:1][C:2]2[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][C:10]([O:12][CH3:13])=[O:11])=[CH:6][CH:7]=2)[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:16][CH2:15]1
Reactant: O[C@@H]1CCc2ccccc21
Reactant: COC(=O)CCc1ccc(O)cc1
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: C1CCOC1
Solvent: O
Product: COC(=O)CCc1ccc(O[C@H]2CCc3ccccc32)cc1
Temperature: -30 °C
Reaction time: 23 h
Yield: 67.5 %

Procedure:
Methyl 4-hydroxybenzenepropanoate (4.1 g, 22 mmol) was dissolved in tetrahydrofuran (50 mL) and the mixture was stirred at −30° C. (R)-1-Indanol (98% ee) (3.0 g, 22 mmol), 1,1′-(azodicarbonyl)dipiperidine (5.66 g, 22 mmol) and tributylphosphine (5.6 mL, 22 mmol) were added and the mixture was stirred at −30° C. for 23 hrs. Water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The mixture was concentrated under reduced pressure and the obtained oil was purified by silica gel chromatography (hexane to hexane/ethyl acetate=10:1) to give the title compound (4.4 g, yield 66%) as a yellow oil.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([CH2:9][C:10]#[N:11])=[C:4]([CH3:12])[CH:3]=1.[Na].Cl.[CH3:15][CH2:16][O:17]C(C)=O>>[Cl:1][C:2]1[CH:3]=[C:4]([CH3:12])[C:5]([CH:9]([C:16](=[O:17])[CH3:15])[C:10]#[N:11])=[C:6]([CH3:8])[CH:7]=1
Reactant: CCOC(C)=O
Reactant: Cc1cc(Cl)cc(C)c1CC#N
Agent: Cl
Agent: [Na]
Product: CC(=O)C(C#N)c1c(C)cc(Cl)cc1C
Temperature: 90 °C

Procedure:
Dissolve 4-chloro-2,6-dimethyl phenyl acetonitrile (2.3 g, 179.2 g/mol) in 15 mL EtOAc and add sodium metal (0.35 g, pea-sized fragments). Heat to reflux (90° C. bath temperature) under N2 overnight. Evaporate down to solid and slurry up in Et2O (100 mL); stir vigorously to break up fragments. Filter and wash solid with copious amounts of Et2O. Dissolve solid in H2O to form a clear yellow solution, and add 1.0 N HCl (100 mL) to pH 1. Extract the resulting cloudy solution with CH2Cl2 (3×100 mL) until aqueous layer is clear. Pool and dry the organic layers over Na2SO4, filter and evaporate to yellow oil (1.8 g). TLC: Rf=0.2 using 20% EtOAc/80% hexanes as eluent. LCMS=222.3 (MH+); 220.2 (M−)
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([N:8]=[C:9]=[S:10])[CH:5]=[CH:6][CH:7]=1.[C:11]([NH:15][C:16](=[O:18])[O-:17])([CH3:14])([CH3:13])[CH3:12].CNC>CO>[OH:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]([N:15]([CH3:16])[CH3:11])=[S:10])[CH:5]=[CH:6][CH:7]=1.[C:11]([NH:15][C:16](=[O:17])[O-:18])([CH3:14])([CH3:13])[CH3:12]
Reactant: Oc1cccc(N=C=S)c1
Agent: CC(C)(C)NC(=O)[O-]
Agent: CNC
Solvent: CO
Product: CN(C)C(=S)Nc1cccc(O)c1
Temperature: 15 °C

Procedure:
1-(meta-hydroxyphenyl)-3,3-dimethyl-2-thiourea, tert-butylcarbamate is prepared by charging to a suitable vessel about 25 g. (approximately 0.1 mole) meta-hydroxyphenyl isothiocyanate, tert-butylcarbamate dissolved in about 150 ml. of methanol, and adding, with stirring about 15.4 g. (approximately 0.12 moles) of 40 percent aqueous dimethylamine mixed with about 50 ml. of methanol in a single increment. The mass quickly solidifies as the temperature rises from about room temperature to about 60° C. The mass is cooled to about 15° C., separated from the residual liquid by filtration, washed with four 150 ml. portions of a 75 percent methanol/25 percent water solution and dried under vacuum overnight.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[CH2:12][CH2:13][N:14]([CH2:17][CH2:18][CH2:19][CH2:20][CH:21]4[C:29]5[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=5)[NH:23][CH2:22]4)[CH2:15][CH:16]=3)=[CH:7][NH:8]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:37](Cl)(=[O:39])[CH3:38]>C1COCC1>[C:37]([N:23]1[C:24]2[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:21]([CH2:20][CH2:19][CH2:18][CH2:17][N:14]2[CH2:13][CH:12]=[C:11]([C:6]3[C:5]4[C:9](=[CH:10][C:2]([Cl:1])=[CH:3][CH:4]=4)[NH:8][CH:7]=3)[CH2:16][CH2:15]2)[CH2:22]1)(=[O:39])[CH3:38]
Reactant: Clc1ccc2c(C3=CCN(CCCCC4CNc5ccccc54)CC3)c[nH]c2c1
Reactant: CC(=O)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(=O)N1CC(CCCCN2CC=C(c3c[nH]c4cc(Cl)ccc34)CC2)c2ccccc21
Temperature: 5 °C
Yield: 49.9 %

Procedure:
A mixture of 6-chloro-3-[1-[4-(2,3-dihydro-1H-indol-3-yl)butan-1-yl]-1,2,3,6-tetrahydropyridin-4-yl]-1H-indole 30b (4.9 g), triethylamine (3.7 g), and THF (200 ml) was cooled (5° C.), and the mixture was added a solution of acetyl chloride (1.0 g) in THF (50 ml). The reaction mixture was allowed to warm to room temperature, filtered and concentrated in vacuo. The residue was purified on silica gel eluted with ethyl acetate-ethanol-triethylamine (90:10:5) to give the crude product, which was recrystallized (methanol-ethyl acetate) to give the title compound (2.7 g).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:15]([NH2:17])=[N:14][CH:13]=[N:12][C:11]=3[N:10]([CH:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)[CH:9]=2)=[CH:4][C:3]=1[O:23][CH3:24].N1C=CC=CC=1.[C:31]1([CH2:37][S:38](Cl)(=[O:40])=[O:39])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>ClCCl>[NH2:17][C:15]1[C:16]2[C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][S:38]([CH2:37][C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)(=[O:40])=[O:39])=[C:3]([O:23][CH3:24])[CH:4]=3)=[CH:9][N:10]([CH:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)[C:11]=2[N:12]=[CH:13][N:14]=1
Reactant: O=S(=O)(Cl)Cc1ccccc1
Reactant: COc1cc(-c2cn(C3CCCC3)c3ncnc(N)c23)ccc1N
Solvent: ClCCl
Solvent: c1ccncc1
Product: COc1cc(-c2cn(C3CCCC3)c3ncnc(N)c23)ccc1NS(=O)(=O)Cc1ccccc1
Reaction time: 8 h
Yield: 22.7 %

Procedure:
5-(4-Amino-3-methoxyphenyl)-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (27 mg, 0.083 mmol) was dissolved in dichloromethane (0.8 mL). Pyridine (0.8 mL) was added followed by phenylmethanesulfonyl chloride (19 mg, 0.105 mmol). After stirring overnight, another 19 mg of phenylmethanesulfonyl chloride was added and the reaction mixture was stirred overnight. The solvent was removed and the residue was purified by preparative thin layer chromatogram eluted with dichlormethane/Methanol (95:5) to give N-[4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl]phenylmethanesulfonamide (9 mg, 0.0188 mmol). 1H NMR (DMSO-d6) δ 1.89 (m, 6H), 2.28 (m, 2H), 3.85 (s, 3H), 4.38 (s, 2H), 5.23 (m, 3H), 6.08 (bs, 1H), 6.99 (m, 2H), 7.27, (m, 2H), 7.33 (m, 3H), 7.58 (d, J=8.17 Hz, 1H), 8.34 (s, 1H). LC/MS MH+=478
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[CH:7][C:6]([Cl:9])=[CH:5][C:3]=1[NH2:4].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Br:20][C:21]1[S:25][C:24]([C:26]#[N:27])=[CH:23][CH:22]=1>C1COCC1>[Br:20][C:21]1[S:25][C:24]([C:26]([NH:4][C:3]2[CH:5]=[C:6]([Cl:9])[CH:7]=[CH:8][C:2]=2[Cl:1])=[NH:27])=[CH:23][CH:22]=1
Reactant: N#Cc1ccc(Br)s1
Reactant: Nc1cc(Cl)ccc1Cl
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: C1CCOC1
Product: N=C(Nc1cc(Cl)ccc1Cl)c1ccc(Br)s1
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 93.3 %

Procedure:
Under N2 atmosphere, to a solution of 2,5-dichloroaniline (341 mg, 2.1 mmol) in 2 mL dry THF was added sodium bis(trimethylsilyl)amide (2.1 mL, 1M solution in THF, 2.1 mmol). After the mixture was stirred at ambient temperature for 40 min, a solution of 5-bromo-thiophene-2-carbonitrile (376 mg, 2 mmol) in 2 mL dry THF was added dropwise. The reaction mixture was stirred overnight, and then poured into 100 mL ice water. The orange precipitate was collected by filtration, washed with a solution of ether and hexane (3/7, v/v), and air dried to give a light orange solid (653 mg, 94% yield). 1H-NMR (400 MHz, MeOH-d4): δ 6.94 (d, 1H), 6.99 (dd, 1H), 7.06 (d, 1H), 7.32 (d, 1H), 7.37 (d, 1H).
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C:6]([CH3:13])([CH3:12])[CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])=[O:4].[NH3:14]>O.C(O)C>[NH2:14][CH2:2][C:3]([NH:5][C:6]([CH3:13])([CH3:12])[CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])=[O:4]
Reactant: CCCCCC(C)(C)NC(=O)CCl
Reactant: N
Solvent: O
Solvent: CCO
Product: CCCCCC(C)(C)NC(=O)CN
Reaction time: 0.5 h

Procedure:
A suspension of 2-Chloro-N-(1,1-dimethylhexyl)acetamide (2.5 g, 12 m mol) in a mixture of water (50 ml) and ethanol (50 ml) was saturated in ammoniain the cold and held at room temperature for two days with the occasional passage of ammonia. The mixture was evaporated to a gum which was partially dried by azeotroping with ethanol then 40-60 petrol. The residuewas dissolved in chloroform (50 ml) and stirred with sodium carbonate (2 g)and water (10 ml) for 1/2 hour. The organic phase was then separated, driedover magnesium sulphate, evaporated to a yellow oil and distilled to give 2-amino-N-(1,1-dimethylhexyl)acetamide as a colourless oil, b.p. 109°-113° C. at 0.4 mm Hg.
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:6][O:7][CH2:8][CH2:9]Cl>>[CH3:6][O:7][CH2:8][CH2:9][N:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: COCCCl
Reactant: C1CCNC1
Product: COCCN1CCCC1
Reaction time: 48 h

Procedure:
In an autoclave of 100 mL, pyrrolidine (40.0 g, 563 mmol) was made reacted with chloroethyl methyl ether (26.0 g, 275 mmol) at 125 deg C. for 48 hours. Solid salt that was formed was removed by filtration, and residue (filtrate) was subjected to reduced-pressure distillation by using a Vigreux column of 25 cm. Then 1H-NMR measurement of obtained amine is performed, and it was confirmed that chemical shifts, δ (ppm), are 3.46-3.43 (t, 2H), 3.30(s, 3H), 2.62-2.59(t, 2H), 2.49-2.46(m, 4H), and 1.73-1.70 (m, 4H), and that N-2-methoxyethylpyrrolidine was synthesized.
Reaction SMILES: [NH2:1][N:2]1[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.[CH3:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:16]=[C:17]([C:28](O)=[O:29])[N:18]([CH3:27])[C:19]=2[C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=2)=[CH:11][CH:10]=1>>[N:2]1([NH:1][C:28]([C:17]2[N:18]([CH3:27])[C:19]([C:20]3[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=3)=[C:15]([C:12]3[CH:11]=[CH:10][C:9]([CH3:8])=[CH:14][CH:13]=3)[N:16]=2)=[O:29])[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1
Reactant: Cc1ccc(-c2nc(C(=O)O)n(C)c2-c2ccc(C)cc2)cc1
Reactant: NN1CCOCC1
Product: Cc1ccc(-c2nc(C(=O)NN3CCOCC3)n(C)c2-c2ccc(C)cc2)cc1

Procedure:
Using essentially the same procedure as Example 9, Step B, but using 4-aminomorpholine (0.025 mL), 4,5-di-(4-methylphenyl)-1-methylimidazole-2-carboxylic acid (25 mg, 0.08 mmol) from Example 9, Step A was converted to the title compound. HPLC/MS: 391 (M+1); Rt=3.12 min.
Reaction SMILES: Cl[CH2:2][Si:3]([C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][CH:7]=1)([CH3:5])[CH3:4].[Na].[NH:14]1[CH:18]=[N:17][CH:16]=[N:15]1>CN(C)C=O.O>[Cl:12][C:9]1[CH:10]=[CH:11][C:6]([Si:3]([CH3:5])([CH3:4])[CH2:2][N:14]2[CH:18]=[N:17][CH:16]=[N:15]2)=[CH:7][CH:8]=1
Reactant: C[Si](C)(CCl)c1ccc(Cl)cc1
Reactant: c1nc[nH]n1
Agent: [Na]
Solvent: CN(C)C=O
Solvent: O
Product: C[Si](C)(Cn1cncn1)c1ccc(Cl)cc1
Yield: 39.7 %

Procedure:
A mixture of 2.2 g (0.010 mol) of chloromethyl(4-chlorophenyl)dimethylsilane and 1.1 g (0.012 mol) of 1,2,4-triazole sodium salt in 5 ml of dimethylformamide was warmed to 80°-90° for 2 hours, diluted with water, and extracted with ether. The ether solution was washed with water and brine, dried over magnesium sulfate, and evaporated to leave 2:1 g (83%) of the title compound as a yellow liquid: nD21 1.5428; ir (neat) 1555, 1470, 1245, 1130, 1080, 1010, 835, 805, 795, 735 cm-1 ; nmr (CDCl3) 0.4 (6H, s), 3.8 (2H, s), 7.4 (4H, broad s), 7.8 (1H, s), 7.9 (1H, s).
Reaction SMILES: [CH2:1]1[O:9][C:8]2[CH:7]=[CH:6][C:5]([CH:10]([CH2:13][CH2:14][CH2:15][CH3:16])[CH2:11][NH2:12])=[CH:4][C:3]=2[O:2]1.[CH:17]([C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH:26]([CH3:28])[CH3:27])[C:21]=1[N:29]=[C:30]=[O:31])([CH3:19])[CH3:18]>CCCCCC>[CH2:1]1[O:9][C:8]2[CH:7]=[CH:6][C:5]([CH:10]([CH2:13][CH2:14][CH2:15][CH3:16])[CH2:11][NH:12][C:30]([NH:29][C:21]3[C:20]([CH:17]([CH3:18])[CH3:19])=[CH:25][CH:24]=[CH:23][C:22]=3[CH:26]([CH3:28])[CH3:27])=[O:31])=[CH:4][C:3]=2[O:2]1
Reactant: CC(C)c1cccc(C(C)C)c1N=C=O
Reactant: CCCCC(CN)c1ccc2c(c1)OCO2
Solvent: CCCCCC
Product: CCCCC(CNC(=O)Nc1c(C(C)C)cccc1C(C)C)c1ccc2c(c1)OCO2
Temperature: 25 °C
Reaction time: 1 h
Yield: 31 %

Procedure:
To 4.8 g (21.7 mmol) of (+)-2-(3,4-methylenedioxyphenyl)hexylamine ([α]D21 =+2.64°, c=0.957, in ethanol), was added 46 ml of a hexane solution (0.472 M) of 2,6-diisopropylphenyl isocyanate, and the mixture was stirred for one hour at room temperature. The precipitated crystals were collected by filtration and recrystallized from ethanol to obtain 2.89 g of (+)- 1-(2-(3,4-methylenedioxyphenyl)hexyl)-3-(2,6-diisopropylphenyl)urea (Yield: 31%).
Reaction SMILES: [CH3:1][C:2]1[C:10]2[NH:9][CH:8]=[N:7][C:6]=2[C:5]([CH3:11])=[CH:4][C:3]=1[N:12]=[C:13]=[S:14].CO.[CH2:17]([NH2:20])[CH2:18][NH2:19]>C(Cl)Cl>[CH3:1][C:2]1[C:10]2[NH:9][CH:8]=[N:7][C:6]=2[C:5]([CH3:11])=[CH:4][C:3]=1[NH:12][C:13]([NH:19][CH2:18][CH2:17][NH2:20])=[S:14]
Reactant: NCCN
Reactant: Cc1cc(N=C=S)c(C)c2[nH]cnc12
Solvent: ClCCl
Solvent: CO
Product: Cc1cc(NC(=S)NCCN)c(C)c2[nH]cnc12
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 4,7-dimethyl-5-benzimidazolylisothiocyanate (0.59 g) in CH2Cl2 (50 mL)/methanol (5 mL) is added dropwise over 20 minutes to ethylenediamine (1 mL) in solution in CH2Cl2 (150 mL). The mixture is stirred for 2 hours at room temperature. The resulting suspension is filtered and the solid is dried overnight in vacuo to afford N-(4,7-dimethyl-5-benzimidazolyl)-N'-2-aminoethylthiourea as a white solid.
Reaction SMILES: C(OC([NH:8][C:9]1[CH:10]=[C:11]([CH:16]=[C:17]([C:19]([CH3:22])([CH3:21])[CH3:20])[CH:18]=1)[C:12]([O:14][CH3:15])=[O:13])=O)(C)(C)C.[C:23](O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:8][C:9]1[CH:10]=[C:11]([CH:16]=[C:17]([C:19]([CH3:22])([CH3:21])[CH3:20])[CH:18]=1)[C:12]([O:14][CH2:15][CH3:23])=[O:13]
Reactant: O=C(O)C(F)(F)F
Reactant: COC(=O)c1cc(NC(=O)OC(C)(C)C)cc(C(C)(C)C)c1
Solvent: ClCCl
Product: CCOC(=O)c1cc(N)cc(C(C)(C)C)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Methyl 3-(tert.-butoxycarbonylamino)-5-tert-butylbenzoate (0.42 g) was dissolved in DCM (5 ml). To the resulting solution, TFA (1 ml) was added, the mixture was stirred for 30 min at room temperature and then concentrated in vacuum. The residue was dissolved in DCM and extracted with aqueous sodium bicarbonate solution. The organic layer was separated, dried over sodium sulphate and concentrated in vacuum to yield ethyl 3-amino-5-tert-butylbenzoate (0.28 g), which was used for the synthesis of example 112 without further purification.
Reaction SMILES: FC(F)(F)C(O)=O.[C:8]([S:11][CH:12]1[CH2:17][CH2:16][NH:15][CH2:14]/[C:13]/1=[CH:18]\[C:19]1[N:23]([CH2:24][C:25]([O:27][CH3:28])=[O:26])[N:22]=[N:21][CH:20]=1)(=[O:10])[CH3:9].Br[CH:30]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[F:42])[C:31]([CH:33]1[CH2:35][CH2:34]1)=[O:32].[ClH:43]>C(N(CC)CC)C>[ClH:43].[C:8]([S:11][CH:12]1[CH2:17][CH2:16][N:15]([CH:30]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=2[F:42])[C:31]([CH:33]2[CH2:34][CH2:35]2)=[O:32])[CH2:14]/[C:13]/1=[CH:18]\[C:19]1[N:23]([CH2:24][C:25]([O:27][CH3:28])=[O:26])[N:22]=[N:21][CH:20]=1)(=[O:10])[CH3:9]
Reactant: COC(=O)Cn1nncc1/C=C1\CNCCC1SC(C)=O
Reactant: O=C(C1CC1)C(Br)c1ccccc1F
Agent: Cl
Solvent: O=C(O)C(F)(F)F
Solvent: CCN(CC)CC
Product: COC(=O)Cn1nncc1/C=C1\CN(C(C(=O)C2CC2)c2ccccc2F)CCC1SC(C)=O
Yield: 50 %

Procedure:
Following a procedure similar to that described in Example 150-(g), (E)-4-(acetylsulfanyl)-3-{[1-(methoxycarbonylmethyl)-1H-1,2,3-triazol-5-yl]methylidene}piperidine hydrogen trifluoroacetate (1.06 g) was subjected to the reaction with 2-bromo-2-(2-fluorophenyl)-1-cyclopropylethanone and triethylamine and the free base that was obtained by silica gel chromatography was similarly treated with hydrogen chloride to yield the title compound (650 mg, yield: 50%) as a pale yellow amorphous solid.
Reaction SMILES: [CH:1](=O)[CH2:2][CH2:3][CH3:4].[Br:6][C:7]1[C:8]([CH3:14])=[C:9]([NH2:13])[CH:10]=[CH:11][CH:12]=1.BrC1C(C)=C(C=CC=1)NCCC>>[Br:6][C:7]1[C:8]([CH3:14])=[C:9]([CH:10]=[CH:11][CH:12]=1)[NH:13][CH2:1][CH2:2][CH2:3][CH3:4]
Reactant: Cc1c(N)cccc1Br
Reactant: CCCC=O
Agent: CCCNc1cccc(Br)c1C
Product: CCCCNc1cccc(Br)c1C

Procedure:
Prepared from butyraldehyde and 3-bromo-2-methylphenylamine using the procedure described Intermediate 56.
Reaction SMILES: [Cl:1][CH:2]=[C:3]([Cl:5])Cl.[Na].[OH:7][C:8]1[CH:9]=[C:10]([CH:15]=[CH:16][CH:17]=1)[C:11]([O:13][CH3:14])=[O:12].C(OCCO)C>C(Cl)Cl>[Cl:5][C:3]([O:7][C:8]1[CH:9]=[C:10]([CH:15]=[CH:16][CH:17]=1)[C:11]([O:13][CH3:14])=[O:12])=[CH:2][Cl:1]
Reactant: ClC=C(Cl)Cl
Reactant: COC(=O)c1cccc(O)c1
Agent: [Na]
Solvent: CCOCCO
Solvent: ClCCl
Product: COC(=O)c1cccc(OC(Cl)=CCl)c1
Temperature: 150 °C
Reaction time: 2 h

Procedure:
185 parts of trichloroethylene are introduced into a suspension of 180 parts of the sodium salt of methyl 3-hydroxybenzoate in 200 parts of ethylene glycol monoethyl ether in an autoclave, and the mixture is stirred for 2 hours at 150° C. The solvent is then stripped off under reduced pressure, the viscous residue is taken up in 300 parts of methylene chloride and the solution is filtered in the presence of active charcoal and is chromatographed over neutral alumina. After removing the methylene chloride under reduced pressure from the whole eluate, the residue is distilled through a Vigreux column at 125°-131° C./0.6 mbar, giving methyl 3-(1',2'-dichlorovinyloxy)-benzoate, of nD25 =1.5419.