Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][CH:6]=1)=[O:4].[C:14]1([S:20]([NH2:23])(=[O:22])=[O:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.CCN=C=NCCCN(C)C.Cl>ClCCl.CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[C:14]1([S:20]([NH:23][C:9]([C:8]2[CH:7]=[CH:6][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:13][CH:12]=2)=[O:11])(=[O:22])=[O:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: NS(=O)(=O)c1ccccc1
Reactant: COC(=O)c1ccc(C(=O)O)cc1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: COC(=O)c1ccc(C(=O)NS(=O)(=O)c2ccccc2)cc1
Reaction time: 18 h
Yield: 97.3 %

Procedure:
4-Methoxycarbonyl-benzoic acid (from Preparation 11) (5.0 g, 28 mmol) was dissolved in 100 mL of anhydrous dichloromethane. After the addition of DMAP (3.39 g, 28 mmol) and benzenesulfonamide (4.36 g, 28 mmol), EDCI (5.85 g, 31 mmol) was gradually added to the stirred mixture. After 18 hours at room temperature, rotary evaporation of the mixture gave a residue which was mixed with ethyl acetate and 1N HCl. The organic phase was washed with water (1×) and brine (2×), dried (Na2SO4), rotary evaporated, and dried at high vacuum to afford 8.7 g (98%) of methyl 4-phenylsulfonamidocarbonyl-benzoate (4--C6H5SO2 --NHCO--C6H4 --COOCH3) as a white solid. A solution of this material (3.2 g, 10 mmol) in 130 mL of dioxane/water (3:1) was cooled to 0° C. 1N Sodium hydroxide was added dropwise, followed by vigorous stirring at 0° C. for 20 minutes, then at room temperature for 2 hours. The mixture was again cooled to 0° C., and then acidified to pH 2 by gradual addition of 1N HCl. The mixture was rotary evaporated, and the aqueous residue was extracted with ethyl acetate (3×). The combined extracts were washed with brine, dried (Na2SO4), rotary evaporated, and dried at high vacuum to afford the product (4--C6H5SO2NHCO--C6H4 --COOH), m.p. 267°-270° C.
Reaction SMILES: [CH:1]1([C:4]2[C:5]([N:13]3[CH2:18][CH2:17][N:16]([C:19]([C:21]4[CH:26]=[CH:25][C:24]([N:27]5[C@H:31]([CH2:32][OH:33])[CH2:30][CH2:29][C:28]5=[O:34])=[CH:23][C:22]=4[F:35])=[O:20])[CH2:15][CH2:14]3)=[N:6][CH:7]=[C:8]([CH:10]3[CH2:12][CH2:11]3)[CH:9]=2)[CH2:3][CH2:2]1.S(C1C=CC(C)=CC=1)(O[CH3:40])(=O)=O>>[CH:1]1([C:4]2[C:5]([N:13]3[CH2:18][CH2:17][N:16]([C:19]([C:21]4[CH:26]=[CH:25][C:24]([N:27]5[C@H:31]([CH2:32][O:33][CH3:40])[CH2:30][CH2:29][C:28]5=[O:34])=[CH:23][C:22]=4[F:35])=[O:20])[CH2:15][CH2:14]3)=[N:6][CH:7]=[C:8]([CH:10]3[CH2:12][CH2:11]3)[CH:9]=2)[CH2:3][CH2:2]1
Reactant: COS(=O)(=O)c1ccc(C)cc1
Reactant: O=C(c1ccc(N2C(=O)CC[C@H]2CO)cc1F)N1CCN(c2ncc(C3CC3)cc2C2CC2)CC1
Product: COC[C@@H]1CCC(=O)N1c1ccc(C(=O)N2CCN(c3ncc(C4CC4)cc3C3CC3)CC2)c(F)c1

Procedure:
Using (S)-1-{4-[4-(3,5-dicyclopropylpyridin-2-yl)piperazine-1-carbonyl]-3-fluorophenyl}-5-hydroxymethylpyrrolidin-2-one (130 mg) described in Example 294 and methyl tosylate (41 μL) and by the reaction and treatment in the same manner as in Example 36, the title compound (8 mg) was obtained.
Reaction SMILES: [Cl:1][C:2]1[C:3]([CH3:22])=[C:4]([Cl:21])[C:5]2[O:10][CH:9]([C:11]([F:14])([F:13])[F:12])[C:8]([C:15]([O:17]CC)=[O:16])=[CH:7][C:6]=2[CH:20]=1.[OH-].[Na+]>C1COCC1.C(O)C>[Cl:1][C:2]1[C:3]([CH3:22])=[C:4]([Cl:21])[C:5]2[O:10][CH:9]([C:11]([F:14])([F:13])[F:12])[C:8]([C:15]([OH:17])=[O:16])=[CH:7][C:6]=2[CH:20]=1
Reactant: CCOC(=O)C1=Cc2cc(Cl)c(C)c(Cl)c2OC1C(F)(F)F
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: Cc1c(Cl)cc2c(c1Cl)OC(C(F)(F)F)C(C(=O)O)=C2
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 77.7 %

Procedure:
The ester from Step 2 (8.39 g 23.6 mmol) was dissolved in THF (30 mL) and ethanol (20 mL), treated with 2.5 N sodium hydroxide (20 mL, 50 mmol), and stirred at room temperature for 3.5 hours. The reaction mixture was concentrated in vacuo, acidified with 3 N HCl, filtered, and recrystallized from ethanol/water to yield a yellow solid (6.0 g, 78%): mp 229.9–230.9° C. 1H NMR (acetone-d6/300 MHz) 7.90 (s, 1H), 7.58 (s, 1H), 6.00 (q, 1H, J=6.8 Hz), 2.50 (s, 3H). FABLRMS m/z 325 (M−H). FABHRMS m/z 324.9636 (M−H, Calc'd 324.9646). Anal. Calc'd for C12H7Cl2F3O3: C, 44.07; H, 2.16; Cl, 21.68. Found: C, 44.06; H, 2.21; Cl, 21.74.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][NH:3][C:2]1=[O:7].[C:8](Cl)(=[O:16])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]>>[C:8]([N:3]1[CH2:4][CH2:5][CH2:6][O:1][C:2]1=[O:7])(=[O:16])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]
Reactant: O=C1NCCCO1
Reactant: CCCCCCCC(=O)Cl
Product: CCCCCCCC(=O)N1CCCOC1=O

Procedure:
This compound was prepared following the procedure of Example 1 wherein tetrahydro-2H-1,3-oxazin-2-one was used in place of 2-oxazolidone and octanoyl chloride was used in the place of lauroyl chloride.
Reaction SMILES: O1CCCC[C@@H]1O[CH2:8][CH2:9][CH2:10][O:11][C:12]1[CH:22]=[CH:21][C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:14][CH:13]=1.O.C1(C)C=CC(S(O)(=O)=[O:31])=CC=1>CO>[OH:31][C@@H:9]([CH3:8])[CH2:10][O:11][C:12]1[CH:13]=[CH:14][C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:21][CH:22]=1
Reactant: CCOC(=O)c1ccc(OCCCO[C@H]2CCCCO2)cc1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Solvent: O
Product: CCOC(=O)c1ccc(OC[C@H](C)O)cc1
Yield: 891.8 %

Procedure:
A mixture of 4.5 g (0.014 mol) of (S)-ethyl 4-(2-tetrahydropyranyloxy)propoxybenzoate, 0.2 g (0.0011 mol) of p-toluenesulfonic acid monohydrate and 45 ml of methanol were refluxed for 1 h. Then the same procedure as in Referential Example 2 was repeated to obtain 2.2 g of the crude product.
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[CH:8]=[CH:7][N:6]=[CH:5][C:4]=1[CH2:9]O.P(Br)(Br)[Br:14].O>C(OCC)C>[Br:14][CH2:9][C:4]1[CH:5]=[N:6][CH:7]=[CH:8][C:3]=1[C:2]([F:12])([F:11])[F:1]
Reactant: OCc1cnccc1C(F)(F)F
Reactant: BrP(Br)Br
Solvent: CCOCC
Solvent: O
Product: FC(F)(F)c1ccncc1CBr
Temperature: 25 °C
Reaction time: 12 h
Yield: 75 %

Procedure:
A solution of 0.6 g (3.4. mmoles) of (4-trifluoromethylpyridin-3-yl)-methanol dissolved in 50 ml of diethyl ether was cooed to −30° C. Thereto was added 1.4 g (5.2 mmoles) of phosphorus tribromide. The mixture was stirred at room temperature for 12 hours to give rise to a reaction. After confirmation of the completion of the reaction, the reaction mixture was poured into water, followed by extraction with ethyl acetate. The resulting organic layer was washed with water and an aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to vacuum distillation to remove the solvent contained therein, to obtain 0.61 g (yield: 75.3%) of 3-bromomethyl-4-trifluoromethylpyridine as a yellow oily substance.
Reaction SMILES: [CH:1]1([CH2:6][C:7]([NH:9][C@H:10]([C:12]([OH:14])=O)[CH3:11])=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:15][CH:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]([CH3:27])([CH3:26])[O:18][C:17]1=[O:28]>>[CH:1]1([CH2:6][C:7]([NH:9][C@H:10]([C:12]([NH:15][CH:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:19]([CH3:26])([CH3:27])[O:18][C:17]2=[O:28])=[O:14])[CH3:11])=[O:8])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: CC1(C)OC(=O)C(N)c2ccccc21
Reactant: C[C@H](NC(=O)CC1CCCC1)C(=O)O
Product: C[C@H](NC(=O)CC1CCCC1)C(=O)NC1C(=O)OC(C)(C)c2ccccc21

Procedure:
Following General Procedure A above using N-(cyclopentylacetyl)-L-alanine and 4-amino-1,1-dimethyl-3-isochromanone, the title compound could be prepared.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([O:9][C:10]2[C:11]([F:35])=[C:12]([CH2:17][NH:18][C:19]([C:21]3[N:25](COCC[Si](C)(C)C)[CH:24]=[N:23][C:22]=3[Cl:34])=[O:20])[CH:13]=[CH:14][C:15]=2[Cl:16])[CH:5]=[C:6]([Cl:8])[CH:7]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([O:9][C:10]2[C:11]([F:35])=[C:12]([CH2:17][NH:18][C:19]([C:21]3[NH:25][CH:24]=[N:23][C:22]=3[Cl:34])=[O:20])[CH:13]=[CH:14][C:15]=2[Cl:16])[CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: C[Si](C)(C)CCOCn1cnc(Cl)c1C(=O)NCc1ccc(Cl)c(Oc2cc(Cl)cc(Br)c2)c1F
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=C(NCc1ccc(Cl)c(Oc2cc(Cl)cc(Br)c2)c1F)c1[nH]cnc1Cl
Temperature: 25 °C
Reaction time: 3 h
Yield: 82.3 %

Procedure:
To a solution of N-({3-[(3-bromo-5-chlorophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)-4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide (120 mg, 0.192 mmol) in DCM (5 ml) was added TFA (1.0 mL) and the mixture was stirred at room temperature for 3 hours. The solvent was removed and the crude material was purified via reverse phase HPLC to give N-({3-[(3-bromo-5-chlorophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)-4-chloro-1H-imidazole-5-carboxamide (78 mg, 0.158 mmol, 82% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.12 (d, 1H), 8.02-8.42 (m, 1H), 7.73 (s, 1H), 7.41-7.54 (m, 1H), 7.32 (t, 1H), 7.08-7.15 (m, 1H), 6.95-7.06 (m, 1H), 4.49 (d, 2H). LC-MS (ES+) m/z 491.87, [M+H].
Reaction SMILES: [CH:1]1([N:7]=[C:8]=[N:9][CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(O)(=[O:19])C=C.C1(CO)C2C(=CC3C(C=2)=CC=CC=3)C=CC=1>CN(C1C=CC=CN=1)C.CN(C1C=CN=CC=1)C.O1CCCC1>[C:8]([NH:7][CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1)([NH:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1)=[O:19]
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Reactant: C=CC(=O)O
Agent: CN(C)c1ccccn1
Agent: CN(C)c1ccncc1
Agent: OCc1cccc2cc3ccccc3cc12
Solvent: C1CCOC1
Product: O=C(NC1CCCCC1)NC1CCCCC1
Reaction time: 24 h

Procedure:
The adhesive was converted to a switchable adhesive. The method used for esterification of the carboxylic acid groups pendant to the prepolymer chain employed a dehydrating agent, dicyclohexylcarbodiimide (DCC). This was used in conjunction with a dimethylaminopyridine catalyst with the reaction proceeding at room temperature. The following general procedure was initially used for the esterification reaction. For Example 9a), 6.09 g of base PSA (containing 0.0068 moles acrylic acid) was placed in a dry jar along with 1.41 g of anthracenemethanol (0.0068 moles), 1.39 g DCC (0.0068 moles) and 0.33 g DMAP (0.00027 moles). Approximately 100 ml of anhydrous tetrahydrofuran (THF) was added to the reaction mixture which was left stirring overnight (˜24 hours). A precipitate was formed as a by-product of the esterification (dicyclohexylurea, DHU) which was insoluble in THF and was therefore filtered from the PSA solution. A viscous yellow liquid was produced which was then spread thinly onto Melinex for UV irradiation.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][C:11](=[CH:15][CH2:16][OH:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)(Cl)Cl>CCCCCC.[O-2].[O-2].[Mn+4]>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][C:11](=[CH:15][CH:16]=[O:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CCCC(=CCO)CC1
Agent: [Mn+4]
Agent: [O-2]
Solvent: CCCCCC
Solvent: ClC(Cl)Cl
Product: CC(C)(C)OC(=O)N1CCCC(=CC=O)CC1
Reaction time: 18 h
Yield: 55.5 %

Procedure:
Manganese dioxide (507 g) was added to a solution of 61 g (0.25 mol) of 4-(2-hydroxyethylidene)azepane-1-carboxylic acid t-butyl ester obtained in the above 2) in a mixture of hexane (1865 ml)-chloroform (624 mL) and stirred for 18 hours. After the reaction was completed, insoluble materials were filtered off through Celite and the filtrate was concentrated under a reduced pressure to obtain 33.2 g (yield 55%) of 4-(2-oxoethylidene)azepane-1-carboxylic acid t-butyl ester (VII-17, 125, 126). Its physical property is shown below.
Reaction SMILES: Br[C:2]1[CH:7]=[N:6][C:5]([Br:8])=[CH:4][N:3]=1.[Cl:9][C:10]1[CH:15]=[C:14]([OH:16])[CH:13]=[CH:12][N:11]=1.C([O-])([O-])=O.[Cs+].[Cs+].O>CN(C=O)C>[Br:8][C:5]1[CH:4]=[N:3][C:2]([O:16][C:14]2[CH:13]=[CH:12][N:11]=[C:10]([Cl:9])[CH:15]=2)=[CH:7][N:6]=1
Reactant: Brc1cnc(Br)cn1
Reactant: Oc1ccnc(Cl)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: Clc1cc(Oc2cnc(Br)cn2)ccn1
Temperature: 70 °C
Yield: 84.1 %

Procedure:
A mixture of 2,5-dibromopyrazine (2.42 g, 10.2 mmol), 2-chloro-4-hydroxy pyridine (1.2 g, 9.3 mmol) and Cs2CO3 (3.02 g, 9.26 mmol) in DMF (15 mL) was heated at 70° C. for 16 h with stirring. The mixture was poured into water (150 mL) and stirred for 15 min. The resultant precipitate was collected by filtration, washed with water (4×4 mL) and dried in vacuo to provide 2-bromo-5-((2-chloropyridin-4-yl)oxy)pyrazine (2.24 g, 84%) as an off-white solid. MS (ESI) m/z: 285.9/287.9 (M+H+).
Reaction SMILES: Br[CH2:2][CH2:3][N:4]1[C:8]([CH2:9]Cl)=[CH:7][C:6]([N+:11]([O-:13])=[O:12])=[N:5]1.[CH3:14][O:15][CH2:16][CH:17]([NH2:19])[CH3:18].CS(C)=O>O>[CH3:14][O:15][CH2:16][CH:17]([N:19]1[CH2:2][CH2:3][N:4]2[N:5]=[C:6]([N+:11]([O-:13])=[O:12])[CH:7]=[C:8]2[CH2:9]1)[CH3:18]
Reactant: O=[N+]([O-])c1cc(CCl)n(CCBr)n1
Reactant: COCC(C)N
Solvent: CS(C)=O
Solvent: O
Product: COCC(C)N1CCn2nc([N+](=O)[O-])cc2C1
Temperature: 120 °C
Yield: 67.5 %

Procedure:
A microwave vial equipped with a magnetic stirrer was charged with 1-(2-bromoethyl)-5-(chloromethyl)-3-nitro-1H-pyrazole 296c (1.0 g, 3.7 mmol), 1-methoxypropan-2-amine (1.0 g, 11.2 mmol), and DMSO (6 mL). The mixture was heated at 120° C. under microwave irradiation for 1.0 h. It was the cooled to room temperature and diluted with water (30 mL). The resulting mixture was extracted with ethyl acetate (3×20 mL). The combined organic layer was dried and concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with petroleum ether/ethyl acetate (60/1 to 1/1) to afford 300a (600 mg, 68%) as a yellow solid. MS-ESI: [M+H]+ 241.0
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][C:4]([NH:7][C:8]([C:10]2[CH:20]=[C:19]([O:21][CH:22]([CH3:24])[CH3:23])[C:13]3[CH2:14][CH:15]([CH2:17][OH:18])[O:16][C:12]=3[CH:11]=2)=[O:9])=[N:3]1.[C:25]1([CH3:35])[CH:30]=[CH:29][C:28]([S:31](Cl)(=[O:33])=[O:32])=[CH:27][CH:26]=1>N1C=CC=CC=1.CN(C1C=CN=CC=1)C>[CH:22]([O:21][C:19]1[C:13]2[CH2:14][CH:15]([CH2:17][O:18][S:31]([C:28]3[CH:29]=[CH:30][C:25]([CH3:35])=[CH:26][CH:27]=3)(=[O:33])=[O:32])[O:16][C:12]=2[CH:11]=[C:10]([C:8](=[O:9])[NH:7][C:4]2[CH:5]=[CH:6][N:2]([CH3:1])[N:3]=2)[CH:20]=1)([CH3:24])[CH3:23]
Reactant: CC(C)Oc1cc(C(=O)Nc2ccn(C)n2)cc2c1CC(CO)O2
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OCC2Cc3c(OC(C)C)cc(C(=O)Nc4ccn(C)n4)cc3O2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 78.1 %

Procedure:
To a solution of 2-hydroxymethyl-4-isopropoxy-2,3-dihydro-benzofuran-6-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide (215) (506 mg, 1.530 mmol) in pyridine (10 mL) was added DMAP (20 mg), followed by p-toluenesulfonyl chloride (533 mg, 2.79 mmol). The mixture was stirred at room temperature overnight. The reaction was quenched with water, extracted with 3× EtOAc, dried over Na2SO4, concentrated and purified by flash column chromatography with 35-60% EtOAc in hexanes to give a white solid (580 mg, 78% yield). 1H NMR (400 MHz, CDCl3) δ 8.38 (s, 1 H) 7.78 (d, J=8.34 Hz, 2 H) 7.35 (d, J=8.08 Hz, 2 H) 7.29 (d, J=2.27 Hz, 1 H) 6.96 (s, 1 H) 6.80 (d, J=2.27 Hz, 1 H) 6.69 (d, J=1.26 Hz, 1 H) 5.01 (dd, J=4.93, 1.89 Hz, 1 H) 4.56-4.66 (m, 1 H) 4.19 (dd, J=5.05, 2.27 Hz, 2 H) 3.81 (s, 3 H) 3.24 (dd, J=16.55, 9.73 Hz, 1 H) 2.95 (dd, J=16.42, 6.82 Hz, 1 H) 2.45 (s, 3 H) 1.30-1.35 (m, 6 H); LCMS for C24H27N3O6S m/z 486.20 (M+H+).
Reaction SMILES: [F:1][C:2]([F:9])([F:8])[C:3]([O:5]CC)=O.C[O-].[Na+].CO.[C:15]1(=[O:25])[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:18][CH2:17][CH2:16]1>CCOCC.Cl>[F:9][C:2]([F:1])([F:8])[C:3]([CH:16]1[CH2:17][CH2:18][C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:15]1=[O:25])=[O:5]
Reactant: O=C1CCCc2ccccc21
Reactant: CCOC(=O)C(F)(F)F
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCOCC
Solvent: CO
Product: O=C1c2ccccc2CCC1C(=O)C(F)(F)F
Temperature: 25 °C
Yield: 66.1 %

Procedure:
A 250 mL one necked round bottomed flask equipped with a reflux condenser, nitrogen inlet and provisions for magnetic stirring was charged with ethyl trifluoroacetate (28.4 g, 0.2 mol) and 75 mL of ether. To this solution was added 48 mL of 25% sodium methoxide in methanol (0.21 mol). A solution of 1-tetralone (29.2 g, 0.2 mol) in 50 mL of ether was added over about 5 minutes. The reaction mixture was stirred at room temperature for 14 hours and was diluted with 100 mL of 3N HCl. The phases were separated and the organic layer was washed with 3N HCl, and with brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was taken up in 70 mL of boiling ethanol/water and cooled to room temperature, whereupon crystals of 2-trifluoroacetyl-1-tetralone formed which were isolated by filtration and air dried to give pure compound (32 g, 81%): mp 48°-49° C.; 1H NMR CDCl3 δ 2.8 (m, 2H), 2.9 (m, 2H), 7.2 (d, j=3.0 Hz, 1H), 7.36 (m, 1H), 7.50 (m, 1H), 7.98 (m, 1H); 19F NMR CDCl3 δ -72.0. EI GC-MS M+=242.
Reaction SMILES: [N:1]([CH2:4][C:5]1[CH:6]=[C:7]([CH:10]=[C:11]([CH2:13][F:14])[CH:12]=1)[CH2:8][OH:9])=[N+:2]=[N-:3].[C:15](Cl)([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)([C:24]1[CH:31]=[CH:30][C:27]([O:28][CH3:29])=[CH:26][CH:25]=1)[C:16]1[CH:23]=[CH:22][C:19]([O:20][CH3:21])=[CH:18][CH:17]=1.CN(C=O)C>N1C=CC=CC=1>[CH3:29][O:28][C:27]1[CH:26]=[CH:25][C:24]([C:15]([O:9][CH2:8][C:7]2[CH:6]=[C:5]([CH:12]=[C:11]([CH2:13][F:14])[CH:10]=2)[CH2:4][N:1]=[N+:2]=[N-:3])([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:16]2[CH:23]=[CH:22][C:19]([O:20][CH3:21])=[CH:18][CH:17]=2)=[CH:31][CH:30]=1
Reactant: COc1ccc(C(Cl)(c2ccccc2)c2ccc(OC)cc2)cc1
Reactant: [N-]=[N+]=NCc1cc(CO)cc(CF)c1
Solvent: c1ccncc1
Solvent: CN(C)C=O
Product: COc1ccc(C(OCc2cc(CF)cc(CN=[N+]=[N-])c2)(c2ccccc2)c2ccc(OC)cc2)cc1
Temperature: 25 °C
Reaction time: 22 h

Procedure:
From a reaction system containing 3-Azidomethyl-5-fluoromethylbenzylalcohol (36) (142 mg, 0.73 mmol), the air was evacuated and then Ar was charged therein. To this were added DMTrCl (323 mg, 0.95 mmol), DMF (2.0 mL), and pyridine (2.0 mL), and stirred for 22 hours at a room temperature. TLC was used to confirm the progress of the reaction. Then, the solvent was removed in vacuo. The residue was subjected to extraction with EtOAc. The organic layer was washed with a saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to remove the solvent. The residue was purified by neutral silica gel column chromatography (hexane:EtOAc=20:1 to 5:1) to isolate
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][NH:7][CH3:8])=[CH:4][CH:3]=1.[CH3:11][N:12]([CH:16]([C:20]1[C:21]([C:26]([F:29])([F:28])[F:27])=[N:22][CH:23]=[N:24][CH:25]=1)[CH:17]([CH3:19])[CH3:18])[C:13](Cl)=[O:14].O>N1C=CC=CC=1>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][N:7]([CH3:8])[C:13]([N:12]([CH3:11])[CH:16]([C:20]2[C:21]([C:26]([F:29])([F:28])[F:27])=[N:22][CH:23]=[N:24][CH:25]=2)[CH:17]([CH3:19])[CH3:18])=[O:14])=[CH:4][CH:3]=1
Reactant: CC(C)C(c1cncnc1C(F)(F)F)N(C)C(=O)Cl
Reactant: CNCc1ccc(Cl)cc1
Solvent: O
Solvent: c1ccncc1
Product: CC(C)C(c1cncnc1C(F)(F)F)N(C)C(=O)N(C)Cc1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 10 h
Yield: 53 %

Procedure:
0.16 g (1.0 mmol) of (4-chlorobenzyl)-methylamine was dissolved in 30 ml of pyridine, and 0.3 g (1.0 mmol) of N-methyl-N-(2-methyl-1-(4-trifluoromethyl-pyrimidin-5-yl)-propyl]-carbamoyl chloride was dropwise added, followed by stirring at room temperature for 10 hours. To the reaction solution, 50 ml of water was added, followed by extraction with diethyl ether. The obtained organic phase was washed twice with 30 ml of a dilute citric acid aqueous solution, followed by drying over anhydrous magnesium sulfate. Diethyl ether was distilled off under reduced pressure, and the obtained crude product was purified by silica gel chromatography (developing solvent/n-hexane:ethyl acetate=8:1 to 3:1) to obtain 0.22 g (yield: 52%) of 1-(4-chlorobenzyl)-1,3-dimethyl-3-[2-methyl-1-(4-trifluoromethyl-pyrimidin-5-yl)-propyl]-urea as colorless crystals (melting point: 95-98° C.).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[C:12](=O)[CH2:13][C:14]([O:16]CC)=O.FC(F)(F)C([O-])=O.[CH2:27]([O:29][C:30]([C:32]1[CH:37]=[CH:36][C:35]([C@@H:38]([NH2+:40][NH2:41])[CH3:39])=[CH:34][CH:33]=1)=[O:31])[CH3:28]>C(#N)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:9])([F:10])[F:11])=[CH:4][C:3]=1[C:12]1[CH2:13][C:14](=[O:16])[N:40]([C@H:38]([C:35]2[CH:36]=[CH:37][C:32]([C:30]([O:29][CH2:27][CH3:28])=[O:31])=[CH:33][CH:34]=2)[CH3:39])[N:41]=1
Reactant: CCOC(=O)CC(=O)c1cc(C(F)(F)F)ccc1F
Reactant: CCOC(=O)c1ccc([C@H](C)[NH2+]N)cc1
Agent: O=C([O-])C(F)(F)F
Solvent: CC#N
Product: CCOC(=O)c1ccc([C@H](C)N2N=C(c3cc(C(F)(F)F)ccc3F)CC2=O)cc1

Procedure:
Ethyl 3-[2-fluoro-5-(trifluoromethyl)phenyl]-3-oxopropanoate (3 g, 9.7 mmol) and {(1S)-1-[4-(ethoxycarbonyl)phenyl]ethyl}hydrazinium trifluoroacetate (2.64 g, 8.2 mmol) were heated in dry acetonitrile (150 ml) to 85° C. for 8 hr. Solvent was evaporated and the residue purified by flash column chromatograph (SiO2, 25% ethyl acetate in hexanes) to give ethyl 4-((1S)-1-{3-[2-fluoro-5-(trifluoromethyl)phenyl]-5-oxo-4,5-dihydro-1H-pyrazol-1-yl}ethyl)benzoate as a white solid. NMR (500 MHz, CDCl3) δ: 1.38 (t, J=7.1, 3H); 1.82 (d, 7.2 Hz, 3H); 3.81 (dd, J=3 Hz, 23.9 Hz, 1H); 3.87 (dd, J=3 Hz, 23.9 Hz, 1H); 4.36 (q, J=7.1 Hz, 2H); 5.60 (q, J=7.2 Hz, 1H); 7.25 (t, J=9.5 Hz, 1H); 7.51 (d, J=8.4 Hz, 2H): 7.66 (br, 1H); 8.03 (d, J=8.4 Hz, 2H); 8.25 (dd, J=1.8 Hz, 6.4 Hz, 1H). MS C21H18F4N2O3
Reaction SMILES: [CH3:1][C:2]([N-:9][CH:10]=[CH:11][N-:12][C:13]([CH3:20])([CH3:19])[CH2:14][C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:8])[CH2:3][C:4]([CH3:7])([CH3:6])[CH3:5].[Li+].[Li+].[Cl:23][SiH:24](Cl)Cl>CCCCCC>[Cl:23][SiH:24]1[N:9]([C:2]([CH3:1])([CH3:8])[CH2:3][C:4]([CH3:5])([CH3:6])[CH3:7])[CH:10]=[CH:11][N:12]1[C:13]([CH3:20])([CH3:19])[CH2:14][C:15]([CH3:18])([CH3:17])[CH3:16]
Reactant: CC(C)(C)CC(C)(C)[N-]C=C[N-]C(C)(C)CC(C)(C)C
Reactant: Cl[SiH](Cl)Cl
Agent: [Li+]
Solvent: CCCCCC
Product: CC(C)(C)CC(C)(C)N1C=CN(C(C)(C)CC(C)(C)C)[SiH]1Cl
Temperature: 25 °C
Reaction time: 3 h
Yield: 90 %

Procedure:
In an argon atmosphere, a dilithium(N,N′-bis(1,1,3,3-tetramethylbutyl)-1,2-vinylenediaminide) solution prepared according to the procedure and reagent quantities described in Reference Example-11 was added to a hexane (150 mL) solution containing 25.00 g (184.6 mmol) of trichlorosilane, and the mixture was stirred at room temperature for 3 hours. Insoluble matters produced were separated by filtration, and the solvent was removed by distillation from the filtrate under atmospheric pressure. The obtained residue was distilled under reduced pressure (distillation temperature: 125° C./85 Pa) to obtain 2-chloro-1,3-bis(1,1,3,3-tetramethylbutyl)-1,3-diaza-2-silacyclopent-4-ene (Si(tOctNCHCHNtOct)(H)Cl) as a pale yellow liquid (yielded amount: 57.22 g, yield: 90%).