Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[C:11]([N:12]([CH3:16])[CH:13]([CH3:15])[CH3:14])=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:17]([O:19][CH3:20])=[O:18])[CH:8]=2)[N:3]=1.[CH3:21][C:22]1[NH:23][C:24]2[C:29]([CH:30]=1)=[CH:28][CH:27]=[C:26](B1OC(C)(C)C(C)(C)O1)[CH:25]=2.C([O-])([O-])=O.[K+].[K+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:16][N:12]([CH:13]([CH3:15])[CH3:14])[C:11]1[C:2]([C:27]2[CH:28]=[C:29]3[C:24](=[CH:25][CH:26]=2)[NH:23][C:22]([CH3:21])=[CH:30]3)=[N:3][C:4]2[C:9]([N:10]=1)=[CH:8][C:7]([C:17]([O:19][CH3:20])=[O:18])=[CH:6][CH:5]=2
Reactant: COC(=O)c1ccc2nc(Cl)c(N(C)C(C)C)nc2c1
Reactant: Cc1cc2ccc(B3OC(C)(C)C(C)(C)O3)cc2[nH]1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: COCCOC
Solvent: O
Product: COC(=O)c1ccc2nc(-c3ccc4[nH]c(C)cc4c3)c(N(C)C(C)C)nc2c1
Temperature: 90 °C
Reaction time: 1 h
Yield: 68.1 %

Procedure:
To a solution of methyl 2-chloro-3-[methyl(propan-2-yl)amino]quinoxaline-6-carboxylate (200 mg, 0.68 mmol) in DME (5.0 mL) and water (2 drops) was added 2-methyl-6-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (352 mg, 1.37 mmol), Pd(PPh3)4 (39 mg, 0.03 mmol), and K2CO3 (189 mg, 1.37 mmol) with stirring for 1 hour at 90° C. under atmosphere of nitrogen. The resulting mixture was concentrated in vacuo to give a residue, which was purified by silica gel column chromatography (1% ethyl acetate in petroleum ether) to give methyl 3-[methyl(propan-2-yl)amino]-2-(2-methyl-1H-indol-5-yl)quinoxaline-6-carboxylate as a light yellow solid (180 mg, 68%).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][OH:9])=[CH:4][CH:3]=1.N1C=CC=CC=1.[C:16]([C:20]1[CH:21]=[C:22]([CH:26]=[CH:27][C:28]=1[O:29][CH3:30])[C:23](Cl)=[O:24])([CH3:19])([CH3:18])[CH3:17].O>C1COCC1>[C:16]([C:20]1[CH:21]=[C:22]([CH:26]=[CH:27][C:28]=1[O:29][CH3:30])[C:23]([O:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([OH:1])=[CH:3][CH:4]=1)=[O:24])([CH3:19])([CH3:17])[CH3:18]
Reactant: COc1ccc(C(=O)Cl)cc1C(C)(C)C
Reactant: OCc1ccc(O)cc1
Solvent: O
Solvent: c1ccncc1
Solvent: C1CCOC1
Product: COc1ccc(C(=O)OCc2ccc(O)cc2)cc1C(C)(C)C
Temperature: 25 °C
Reaction time: 24 h

Procedure:
1.24 g (0.01 mol) of 4-hydroxybenzenemethanol, 1 ml (0.01 mol) of pyridine and 50 ml of THF are introduced into a round-bottomed flask. While cooling in an icebath, a solution of 2.2 g (0.01 mol) of 3-tert-butyl-4-methoxybenzoyl chloride in 50 ml of THF is introduced dropwise and the mixture is stirred at room temperature for 24 h. The reaction medium is poured into water, the mixture is extracted with ethyl ether and the organic phase is separated after settling has taken place, dried over magnesium sulphate and evaporated. The residue obtained is purified by chromatography on a silica column and eluted with a mixture of dichloromethane and ethyl ether (97:3).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N+:8]([C:11]1[CH:19]=[CH:18][C:14]([C:15](O)=[O:16])=[CH:13][CH:12]=1)([O-:10])=[O:9].ClC1C=C([N+]([O-])=O)C=CC=1C(O)=O>C1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:15](=[O:16])[C:14]2[CH:13]=[CH:12][C:11]([N+:8]([O-:10])=[O:9])=[CH:19][CH:18]=2)=[CH:4][CH:3]=1
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1
Reactant: Clc1ccccc1
Agent: O=C(O)c1ccc([N+](=O)[O-])cc1Cl
Solvent: c1ccccc1
Product: O=C(c1ccc(Cl)cc1)c1ccc([N+](=O)[O-])cc1
Yield: 36 %

Procedure:
The procedure of Example 21 is repeated in every detail except that a chlorobenzene solution of 4-nitrobenzoic acid is employed in lieu of a benzene solution of 2-chloro-4-nitrobenzoic acid to obtain a 36% yield of 4'-chloro-4-nitrobenzophenone having a melting point equal to 100° C. to 101° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[S:10][CH:9]=[N:8][C:7]=2[CH:11]=1.C(O[C:17](=O)[NH:18][C@H:19]1[CH2:24][CH2:23][C@H:22]([C:25](=[O:30])N(OC)C)[CH2:21][CH2:20]1)(C)(C)C.[O:32]1[C:37]2[CH:38]=[CH:39][C:40](C=O)=[CH:41][C:36]=2[O:35][CH2:34][CH2:33]1>>[O:32]1[C:37]2[CH:38]=[CH:39][C:40]([CH2:17][NH:18][C@H:19]3[CH2:20][CH2:21][C@H:22]([C:25]([C:9]4[S:10][C:6]5[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:11][C:7]=5[N:8]=4)=[O:30])[CH2:23][CH2:24]3)=[CH:41][C:36]=2[O:35][CH2:34][CH2:33]1
Reactant: COc1ccc2scnc2c1
Reactant: O=Cc1ccc2c(c1)OCCO2
Reactant: CON(C)C(=O)[C@H]1CC[C@H](NC(=O)OC(C)(C)C)CC1
Product: COc1ccc2sc(C(=O)[C@H]3CC[C@H](NCc4ccc5c(c4)OCCO5)CC3)nc2c1

Procedure:
Using 5-methoxy-benzothiazole (5 mmol; Tetrahedron (1997), 53, 17029), [trans-4-(methoxy-methyl-carbamoyl)-cyclohexyl]-carbamic acid tert-butyl ester (2.5 mmol) and 2,3-dihydro-benzo[1,4]dioxine-6-carbaldehyde (0.3 mmol) according to the same protocol as that described for example 1, steps 1.a to 1.c, the title compound was obtained as a yellowish solid (92 mg).
Reaction SMILES: C(OP(OCC)(O[CH:7]([CH3:16])/[CH:8]=[C:9](\[CH3:15])/[C:10]([O:12][CH2:13][CH3:14])=[O:11])=O)C.[CH2:20]([NH2:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CCOC(C)=O.CCCCCCC>C(Cl)Cl.[Pd]>[NH3:27].[CH2:20]([NH:27][CH:7]([CH3:16])/[CH:8]=[C:9](\[CH3:15])/[C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: NCc1ccccc1
Reactant: CCOC(=O)/C(C)=C/C(C)OP(=O)(OCC)OCC
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: ClCCl
Solvent: CCCCCCC
Product: CCOC(=O)/C(C)=C/C(C)NCc1ccccc1
Product: N
Yield: 66.5 %

Procedure:
Reaction of 17 (rac-Ethyl (2E)-4-(diethoxyphosphinyloxy)-2-methylpent-2-enoate) (188 mg, 0.60 mind) with BnNH2 (131 μL, 1.2 mmol) and 5 mol % [Pd] in CH2Cl2 (3.5 ml) at room temperature. MPLC (SiO2 with NH3 deactivated, AcOEt:heptane fraction 20:80) and preparative TLC (NH3-conditioned, AcOEt:heptane fraction 50:50) yield 18 (rac-Ethyl (2E)-N-benzyl-4-amino-2-methylpent-2-enoate) (98.7 mg, 67%) as a yellow oil.
Reaction SMILES: Cl[C:2]1[C:3]([N+:8]([O-:10])=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1.[C:11]1([SH:17])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.O>[N+:8]([C:3]1[C:2]([S:17][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:7][CH:6]=[CH:5][N:4]=1)([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1ncccc1Cl
Reactant: Sc1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CS(C)=O
Solvent: O
Product: O=[N+]([O-])c1ncccc1Sc1ccccc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 70 %

Procedure:
3-chloro-2-nitropyridine (30.6 g, 193 mmol) was dissolved in DMSO (200 mL). Benzenethiol (20.7 mL, 203 mmol) was added followed by cesium carbonate (69.3 g, 212 mmol) and stirred at ambient temperature for 1.5 hours. The solution was diluted with water (750 mL) and the solids filtered. The crude material was recrystallized from EtOAc (400 mL) and with adding hexanes (1L) to give an A-crop of 23.5 g. The filtrate was concentrated and recrystallized from EtOAc/hexanes to give 7.87 g. The solids were dried on high vacuum to provide the title compound (31.38 g, 69.8% yield).
Reaction SMILES: [C:1]1([Mg]Br)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:9][C:10]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:11]=1[C:12]#N.Cl.[OH-:21].[Na+]>C(OCC)C>[NH2:9][C:10]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:11]=1[C:12]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[O:21]
Reactant: Br[Mg]c1ccccc1
Reactant: [OH-]
Reactant: COc1ccc(C#N)c(N)c1
Agent: Cl
Agent: [Na+]
Solvent: CCOCC
Product: COc1ccc(C(=O)c2ccccc2)c(N)c1
Temperature: 0 °C
Yield: 85 %

Procedure:
A solution of phenylmagnesium bromide (6.75 ml, 3M solution in diethyl ether, 20.2 mmol) in diethyl ether (15 ml) was added dropwise to a solution of 2-amino-4-methoxybenzonitrile (1000 mg, 6.75 mmol) in diethyl ether (20 ml) at 0° C. The resulting suspension was heated to reflux for 2 h. The mixture was then cooled to 0° C. and 2N HCl (40 ml) was added very carefully. After complete addition, the mixture was heated to 55° C. for 2 h. Then 3N NaOH (˜20 ml) was added at 0° C. to adjust the pH to 9. The mixture was extracted with EtOAc and the combined organic extracts were washed with brine, dried with Na2SO4 and evaporated. The remaining residue was purified by column chromatography (silica gel, heptane/EtOAc 85:15-70:30) to afford the title compound (1300 mg, 85%) as yellow solid. MS (ESI): 228.4 (M+H)+.
Reaction SMILES: [CH2:1]([Li])[CH2:2][CH2:3][CH3:4].[N+:6]([C:9]1[CH:16]=[CH:15][C:12]([CH:13]=O)=[CH:11][CH:10]=1)([O-:8])=[O:7]>O1CCCC1>[CH:13]([C:12]1[CH:15]=[CH:16][C:9]([N+:6]([O-:8])=[O:7])=[CH:10][CH:11]=1)=[CH:4][CH2:3][CH2:2][CH2:1][CH2:11][CH2:10][CH2:9][CH2:16][CH3:15]
Reactant: [Li]CCCC
Reactant: O=Cc1ccc([N+](=O)[O-])cc1
Solvent: C1CCOC1
Product: CCCCCCCCC=Cc1ccc([N+](=O)[O-])cc1
Reaction time: 1 h

Procedure:
phosphonium salt (141 g) obtained from n-nonyl bromide (115 ml) and triphenylphosphine (78.5 g) was dissolved in dry tetrahydrofuran (500 ml) and thereto was dropwise added n-butyl lithium (372 ml, 1.6M hexane solution) over not less than 1 hour at 0° C. After the dropwise addition, the reaction mixture was stirred at said temperature for 30 minutes and at room temperature for 1 hour. A solution of 4-nitrobenzaldehyde (45.3 g) in tetrahydrofuran (150 ml) was dropwise added thereto at 0° C. over 1 hour. The reaction mixture was stirred at room temperature for 10 hours and filtered. The residue was washed with ether. The filtrate was concentrated under reduced pressure and purified by silica gel column chromatography (hexane/ethyl acetate=100:1) to give 70.9 g of 4-(1-decenyl)nitrobenzene (cis/trans=7:3).
Reaction SMILES: [CH3:1][N:2]1[C:7](=[O:8])[C:6]2=[C:9]([S:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=3)[N:10]([CH2:12][C:13]3[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[CH:16]=[CH:15][CH:14]=3)[CH:11]=[C:5]2[N:4]([CH2:30][CH:31]([CH3:33])[CH3:32])[C:3]1=[O:34].S([O-])(O[O-])(=O)=[O:36].[K+].[K+].OOS([O-])=O.[K+]>>[CH3:1][N:2]1[C:7](=[O:8])[C:6]2=[C:9]([S:23]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=3)=[O:36])[N:10]([CH2:12][C:13]3[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[CH:16]=[CH:15][CH:14]=3)[CH:11]=[C:5]2[N:4]([CH2:30][CH:31]([CH3:32])[CH3:33])[C:3]1=[O:34]
Reactant: O=S(=O)([O-])O[O-]
Reactant: CC(C)Cn1c(=O)n(C)c(=O)c2c(Sc3ccccn3)n(Cc3cccc4ccccc34)cc21
Agent: O=S([O-])OO
Agent: [K+]
Product: CC(C)Cn1c(=O)n(C)c(=O)c2c(S(=O)c3ccccn3)n(Cc3cccc4ccccc34)cc21

Procedure:
Prepared from the compound of Example 20, 3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)-5-[(2-pyridinyl)thio]-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione and potassium peroxymonosulphate (commercially sold under the trade mark “OXONE”) following the method of Example 8 c).
Reaction SMILES: [CH3:1][C:2]1([CH3:16])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[C:11]([CH:13]=[CH:14][CH:15]=2)[NH2:12])[O:3]1.C(N(CC)CC)C.[CH2:24]([N:26]=[C:27]=[O:28])[CH3:25]>C1COCC1.C(OCC)C>[CH2:24]([NH:26][C:27]([NH:12][C:11]1[CH:13]=[CH:14][CH:15]=[C:9]([B:4]2[O:3][C:2]([CH3:16])([CH3:1])[C:6]([CH3:7])([CH3:8])[O:5]2)[CH:10]=1)=[O:28])[CH3:25]
Reactant: CCN=C=O
Reactant: CC1(C)OB(c2cccc(N)c2)OC1(C)C
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: CCNC(=O)Nc1cccc(B2OC(C)(C)C(C)(C)O2)c1
Temperature: 60 °C
Yield: 85.5 %

Procedure:
To a solution of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (30 g, 137 mmol, 1.0 equiv) in THF (300 ml) was added triethylamine (58 ml, 410 mmol, 3.0 equiv) and ethyl isocyanate (16.3 ml, 205 mmol, 1.5 equiv). The reaction was warmed to 60° C. for 2 hours. The reaction was cooled to room temperature and diluted with diethyl ether (600 ml). The precipitate was filtered and solid was washed with diethylether to afford desired product 34 g.
Reaction SMILES: [C:1]1([C:11]2[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.Br[C:21]1[C:34]2[C:35]3=[C:36]4[C:31](=[CH:32][CH:33]=2)[CH:30]=[CH:29][CH:28]=[C:27]4[CH:26]=[CH:25][C:24]3=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC>[C:1]1([C:11]2[CH:16]=[CH:15][C:14]([C:28]3[C:27]4[C:36]5=[C:35]6[C:24](=[CH:25][CH:26]=4)[CH:23]=[CH:22][CH:21]=[C:34]6[CH:33]=[CH:32][C:31]5=[CH:30][CH:29]=3)=[CH:13][CH:12]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: Brc1ccc2ccc3cccc4ccc1c2c34
Reactant: OB(O)c1ccc(-c2cccc3ccccc23)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: c1ccc2c(-c3ccc(-c4ccc5ccc6cccc7ccc4c5c67)cc3)cccc2c1
Yield: 99.3 %

Procedure:
7.4 g of 4-(naphthalene-1-yl)phenyl boronic acid prepared by a well known method and 7.0 g of conventional 1-bromopyrene were dissolved in 80 ml of dimethoxyethane (DME). Subsequently, 0.58 g of tetrakistriphenylphosphine palladium and 40 ml of 2M-sodium carbonate aqueous solution were added therein, followed by argon displacement. After heating and refluxing over 8 hours, it was stood to cool and then an organic layer was extracted therefrom by toluene. The organic layer was washed by saturated salt water, followed by drying through anhydrous sodium sulfate, and then the organic solvent was removed by an evaporator. The residue was refined through a silica gel chromatography (a developing solvent: toluene) and then 10.0 g of 1-(4-naphthalene-1-yl-phenyl) pyrene was obtained. (yield: 99%)
Reaction SMILES: N[CH2:2][CH2:3][CH2:4][C:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:6].[ClH:13].[NH:14]([C:21]1[C:30]2[C:25](=[CH:26][CH:27]=[C:28]3[N:33]=[CH:32][NH:31][C:29]3=2)[N:24]=[C:23]([CH3:34])[CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C(O)C>[OH2:6].[ClH:13].[C:5]([C:7]1[CH:12]=[CH:11][C:10]([NH:14][C:21]2[C:30]3[C:25](=[CH:26][CH:27]=[C:28]4[N:33]=[CH:32][NH:31][C:29]4=3)[N:24]=[C:23]([CH3:34])[CH:22]=2)=[CH:9][CH:8]=1)(=[O:6])[CH2:4][CH2:3][CH3:2].[C:5]([C:18]1[CH:19]=[CH:20][C:15]([NH:14][C:21]2[C:30]3[C:25](=[CH:26][CH:27]=[C:28]4[N:33]=[CH:32][NH:31][C:29]4=3)[N:24]=[C:23]([CH3:34])[CH:22]=2)=[CH:16][CH:17]=1)(=[O:6])[CH2:4][CH2:3][CH3:2].[ClH:13]
Reactant: NCCCC(=O)c1ccccc1
Reactant: Cc1cc(Nc2ccccc2)c2c(ccc3nc[nH]c32)n1
Agent: Cl
Solvent: CCO
Product: CCCC(=O)c1ccc(Nc2cc(C)nc3ccc4nc[nH]c4c23)cc1
Product: O

Procedure:
A mixture of 16.3 g. (0.1 m) of 4-aminobutyrophenone, 21.7 g. (0.1 m) of the compound of Example I, C. and 500 ml. of ethanol was refluxed overnight. The solution was concentrated in vacuo to dryness. The soft, yellow solid was dissolved in 300 ml. of MeOH and filtered. The MeOH filtrate was evaporated to a volume of 50 ml. then chilled. The product was filtered, washed with ether and oven-dried (110°C) to give 24 g. m.p. 209°-230°C. A second recrystallization from MeOH yielded 22 g., m.p. 205°-235°C.
Reaction SMILES: [H-].[Na+].CN(C=O)C.[F:8][C:9]([F:13])([F:12])[CH2:10][OH:11].F[C:15]1[CH:16]=[N:17][CH:18]=[CH:19][C:20]=1[C:21]1[O:22][C:23]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][C:24]=2[N:25]=1>O>[F:8][C:9]([F:13])([F:12])[CH2:10][O:11][C:15]1[CH:16]=[N:17][CH:18]=[CH:19][C:20]=1[C:21]1[O:22][C:23]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][C:24]=2[N:25]=1
Reactant: Fc1cnccc1-c1nc2cc(C(F)(F)F)ccc2o1
Reactant: OCC(F)(F)F
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: FC(F)(F)COc1cnccc1-c1nc2cc(C(F)(F)F)ccc2o1
Temperature: 25 °C
Yield: 75.1 %

Procedure:
A mixture of 0.06 g of 55% sodium hydride (in oil) and 2 ml of DMF was stirred at room temperature. To the mixture, a mixture solution of 0.13 g of 2,2,2-trifluoroethanol and 0.5 ml of DMF was added. The mixture solution was stirred at the same temperature for 15 minutes, and then 0.28 g of 2-(3-fluoropyridin-4-yl)-5-(trifluoromethyl)benzoxazole was stirred at room temperature for one hour. Water was added to the reaction mixture, which followed by extraction with ethyl acetate twice. The combined organic layers were washed with a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 0.27 g of 2-[3-(2,2,2-trifluoroethyl)oxypyridin-4-yl]-5-(trifluoromethyl)benzoxazole (hereinafter, referred to as “active compound 39”).
Reaction SMILES: [CH3:1][NH:2][S:3]([C:6]1(Cl)[NH:10][C:9]([Cl:11])=[CH:8][S:7]1)(=[O:5])=[O:4].[CH:13]([NH2:16])([CH3:15])[CH3:14]>C1(C)C=CC=CC=1>[CH3:1][N:2]([NH:16][CH:13]([CH3:15])[CH3:14])[S:3]([C:6]1[S:7][CH:8]=[C:9]([Cl:11])[N:10]=1)(=[O:5])=[O:4]
Reactant: CNS(=O)(=O)C1(Cl)NC(Cl)=CS1
Reactant: CC(C)N
Solvent: Cc1ccccc1
Product: CC(C)NN(C)S(=O)(=O)c1nc(Cl)cs1

Procedure:
In analogy to Example 5, the N-methyl-2-N-isopropylamino-4-chlorothiazole-sulphonamide was prepared by reacting N-methyl-2,4-dichlorothiazole-sulphomamide from Example 2 with a 65% strength aqueous isopropylamine solution. Following recrystallization from toluene, 89% yield of product of m.p. 135° C. were obtained.
Reaction SMILES: [NH2:1][C:2]1[CH:18]=[CH:17][C:5]([CH:6]=[C:7]2[C:15]3[C:10](=[N:11][CH:12]=[CH:13][CH:14]=3)[NH:9][C:8]2=[O:16])=[CH:4][CH:3]=1.[S:19](Cl)([CH3:22])(=[O:21])=[O:20]>N1C=CC=CC=1>[S:19]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([CH:6]=[C:7]2[C:15]3[C:10](=[N:11][CH:12]=[CH:13][CH:14]=3)[NH:9][C:8]2=[O:16])=[CH:17][CH:18]=1)([CH3:22])(=[O:21])=[O:20]
Reactant: CS(=O)(=O)Cl
Reactant: Nc1ccc(C=C2C(=O)Nc3ncccc32)cc1
Solvent: c1ccncc1
Product: CS(=O)(=O)Nc1ccc(C=C2C(=O)Nc3ncccc32)cc1
Temperature: 0 °C
Reaction time: 5 h
Yield: 70 %

Procedure:
To a stirred solution of 3-(4-aminobenzylidene)-7-azaoxindol (2.373 g, 10 mmol) in pyridine (10 ml) was added gradually mesylchloride (1.146 g, 10 mmol) at 0°-5° C. under cooling. The reaction mixture was stirred for about 5 h at 0°-5° C. and then for 15 h at room temperature. The mixture was poured onto an ice-water mixture, the precipitate filtered off, the residue washed thoroughly with water and then chromatographed on silica gel using CHC3 -MeOH mixtures as eluant. Thus pure title compound was obtained in about 70% yield.
Reaction SMILES: O1CCOCC1.[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([CH:14]2[S:18][C:17](=[O:19])[NH:16][C:15]2=[O:20])=[CH:10][CH:9]=1.[C:21](Cl)(=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C(N(CC)CC)C>[C:21]([NH:7][C:8]1[CH:9]=[CH:10][C:11]([CH:14]2[S:18][C:17](=[O:19])[NH:16][C:15]2=[O:20])=[CH:12][CH:13]=1)(=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: Nc1ccc(C2SC(=O)NC2=O)cc1
Reactant: O=C(Cl)c1ccccc1
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: O=C1NC(=O)C(c2ccc(NC(=O)c3ccccc3)cc2)S1
Temperature: 0 °C
Yield: 93.3 %

Procedure:
Into 20 ml of dioxane were dissolved 0.5 g of 5-(4-aminophenyl) thiazolidine-2,4-dione, and, after added 0.34 g of benzoyl chloride and further added dropwise 0.24 g of triethylamine, the mixture was refluxed for 1 hour. After cooling by standing, the reaction mixture was poured into 150 ml of ice water and the crystals deposited were collected by filtration, washed with water and dried. These were recrystallized from chloroform to obtain 0.70 g of title compound.
Reaction SMILES: C[C@H](N)C1C=CC=CC=1.[O:10]([C:17]1[CH:18]=[C:19]([CH:25]=[CH:26][CH:27]=1)[CH:20]([OH:24])[C:21]([OH:23])=[O:22])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>C(O)(C)C>[O:10]([C:17]1[CH:18]=[C:19]([CH:25]=[CH:26][CH:27]=1)[C@H:20]([OH:24])[C:21]([OH:23])=[O:22])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: O=C(O)C(O)c1cccc(Oc2ccccc2)c1
Agent: C[C@H](N)c1ccccc1
Solvent: CC(C)O
Product: O=C(O)[C@@H](O)c1cccc(Oc2ccccc2)c1
Reaction time: 24 h

Procedure:
l-(-)-α-Methylbenzylamine (21.0 g) was added to a solution of racemic 3-phenoxymandelic acid (67.0 g) in isopropyl alcohol (700 ml) and the mixture kept for 24 hours at the ambient temperature. The solid precipitate was collected by filtration, (the filtrate kept--see below) and recrystallised twice from isopropyl alcohol (200 ml) to yield the l-(-)-α-methylbenzylammonium salt of (S)-3-phenoxymandelic acid, m.p. 153° C. This was then shaken with a mixture of diethyl ether 150 ml) and 5N hydrochloric acid (25 ml), the ether layer separated, washed with water, dried over anhydrous magnesium sulphate and concentrated by evaporation of the ether under reduced pressure to yield a residue of solid (S)-3-phenoxymandelic acid, m.p. 110°-112° C., [α]D25 +85° (C, 1.5, methanol).
Reaction SMILES: [C:1]([N:8]([CH3:28])[CH:9]1[CH2:14][CH2:13][CH:12]([NH:15][CH2:16][C:17]2[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][C:22]=2[O:23][CH3:24])[CH2:11][CH2:10]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Br[C:30]1[CH:35]=[CH:34][C:33]([S:36][CH3:37])=[CH:32][CH:31]=1.[Cl:38][C:39]1[C:40]2[C:50]([F:51])=[CH:49][CH:48]=[C:47]([F:52])[C:41]=2[S:42][C:43]=1[C:44](Cl)=[O:45]>>[Cl:38][C:39]1[C:40]2[C:50]([F:51])=[CH:49][CH:48]=[C:47]([F:52])[C:41]=2[S:42][C:43]=1[C:44]([N:15]([CH2:16][C:17]1[CH:18]=[C:19]([C:30]2[CH:35]=[CH:34][C:33]([S:36][CH3:37])=[CH:32][CH:31]=2)[CH:20]=[CH:21][C:22]=1[O:23][CH3:24])[CH:12]1[CH2:13][CH2:14][CH:9]([N:8]([CH3:28])[C:1](=[O:2])[O:3][C:4]([CH3:7])([CH3:6])[CH3:5])[CH2:10][CH2:11]1)=[O:45]
Reactant: COc1ccc(B(O)O)cc1CNC1CCC(N(C)C(=O)OC(C)(C)C)CC1
Reactant: O=C(Cl)c1sc2c(F)ccc(F)c2c1Cl
Reactant: CSc1ccc(Br)cc1
Product: COc1ccc(-c2ccc(SC)cc2)cc1CN(C(=O)c1sc2c(F)ccc(F)c2c1Cl)C1CCC(N(C)C(=O)OC(C)(C)C)CC1

Procedure:
Boronic acid 4 (200 mg, 0.51 mmol) is coupled to 4-bromothioanisole (104 mg, 0.51 mmol) using Method A. On filtration of the cooled reaction mixture through celite and removal of the solvents in vacuo, the crude biaryl amine is treated with acid chloride 8 (163 mg, 0.61 mmol) using Method D to give the title compound.
Reaction SMILES: [Si:1]([O:18][C:19]1[CH:20]=[C:21]([C:25]([C:27]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[NH:29][N:28]=2)=[O:26])[CH:22]=[CH:23][CH:24]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].I[CH2:39][CH:40]([CH3:42])[CH3:41].CCCCCC.C(OCC)(=O)C>CN(C=O)C>[C:14]([Si:1]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[O:18][C:19]1[CH:20]=[C:21]([C:25]([C:27]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[N:29]([CH2:39][CH:40]([CH3:42])[CH3:41])[N:28]=2)=[O:26])[CH:22]=[CH:23][CH:24]=1)([CH3:16])([CH3:17])[CH3:15]
Reactant: CC(C)CI
Reactant: CC(C)(C)[Si](Oc1cccc(C(=O)c2n[nH]c3ccccc23)c1)(c1ccccc1)c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CCCCCC
Product: CC(C)Cn1nc(C(=O)c2cccc(O[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)c2)c2ccccc21
Yield: 85.7 %

Procedure:
(3-{[tert-butyl(diphenyl)silyl]oxy}phenyl)(1H-indazol-3-yl)methanone (0.67 g, 0.0014 mol) was dissolved in DMF (10 mL). Sodium hydride (66%, 0.042 g, 0.0017 mol) was added, and the reaction was stirred until gas evolution stops. 1-iodo-2-methylpropane (0.242 mL, 0.0021 mol) was added. The reaction was stirred at room temperature overnight. The reaction is quenched with water and extracted with ethyl acetate. The desired product (0.650 g, 0.0012 mol, 87%) is isolated by chromatography with hexane/ethyl acetate (10:1).
Reaction SMILES: [CH3:1][C:2]1[CH:15]=[C:5]2[N:6]=[C:7]([CH3:14])[CH:8]=[C:9]([NH:10][CH2:11][CH2:12][NH2:13])[N:4]2[N:3]=1.[C:16]1(=O)[CH2:20][CH2:19][CH2:18][CH2:17]1.C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[CH:16]1([NH:13][CH2:12][CH2:11][NH:10][C:9]2[N:4]3[N:3]=[C:2]([CH3:1])[CH:15]=[C:5]3[N:6]=[C:7]([CH3:14])[CH:8]=2)[CH2:20][CH2:19][CH2:18][CH2:17]1
Reactant: O=C1CCCC1
Reactant: Cc1cc(NCCN)n2nc(C)cc2n1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: Cc1cc(NCCNC2CCCC2)n2nc(C)cc2n1
Reaction time: 1 h
Yield: 128 %

Procedure:
To a stirred solution of N-(2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl)-ethane-1,2-diamine (3.2 g, 16 mmol) and cyclopentanone (2.7 mL, 30 mmol) in methanol (30 mL)/acetic acid (3 mL) was added sodium cyanoborohydride (0.94 g, 15 mmol), portionwise. After stirring 1 hour the reaction was concentrated under reduced pressure and then extracted from saturated aqueous sodium bicarbonate with ethyl acetate. The combined extracts were dried (Na2SO4), concentrated under reduced pressure to give the crude product as a brown oil (5.6 g): +APcI MS (M+1)+ 274; 1H NMR (CDCl3) δ: 6.11 (s, 1H), 6.76 (s, 1H), 3.21 (t, 2H), 3.21 (m, 1H ), 3.04 (t, 1H), 2.42 (s, 3H), 2.40 (s, 3H).