Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([C@:12]1([CH3:18])[CH2:16][O:15][C:14](=[O:17])[NH:13]1)[CH:6]=[CH:5]2.C(=O)([O-])[O-].[Cs+].[Cs+].CS(O[C@H:30]1[CH2:35][CH2:34][C@@H:33]([C:36]([F:39])([F:38])[CH3:37])[CH2:32][CH2:31]1)(=O)=O.O>CC(O)(C)C.CC(=O)CC>[F:38][C:36]([C@H:33]1[CH2:34][CH2:35][C@H:30]([O:1][C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[CH:8]=[C:7]([C@:12]2([CH3:18])[CH2:16][O:15][C:14](=[O:17])[NH:13]2)[CH:6]=[CH:5]3)[CH2:31][CH2:32]1)([F:39])[CH3:37]
Reactant: CC(F)(F)[C@H]1CC[C@@H](OS(C)(=O)=O)CC1
Reactant: C[C@@]1(c2ccc3cc(O)ccc3c2)COC(=O)N1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CCC(C)=O
Solvent: CC(C)(C)O
Product: CC(F)(F)[C@H]1CC[C@H](Oc2ccc3cc([C@]4(C)COC(=O)N4)ccc3c2)CC1
Temperature: 110 °C
Reaction time: 0.17 h

Procedure:
(R)-4-(6-Hydroxynaphthalen-2-yl)-4-methyloxazolidin-2-one (121 mg, 0.5 mmol, 0.9 eq.) and cesium carbonate (407 mg, 1.25 mmol, 2.5 eq.) were dissolved in t-BuOH/2-butanone (10 mL/5 mL). The mixture was stirred at 110° C. for 10 min, then cis-4-(1,1-difluoroethyl)cyclohexyl methanesulfonate (145 mg, 0.6 mmol, 1.1 eq.) was added to the mixture and the mixture was stirred at 110° C. for 15 h. Water was added to the mixture and the mixture was extracted with EtOAc. The organic layer was concentrated and purified by is silica gel column chromatography using petroleum ether/ethyl acetate (1/1) as eluent to give product (203 mg, 58%) as a slight yellow solid. EDI-MS (M+1): 390.1. 1H NMR (400 MHz, CDCl3) δ 7.75-7.72 (m, 3H), 7.42 (dd, 1H), 7.16-7.14 (m, 2H), 6.14 (s, 1H), 4.42 (s, 2H), 4.34-4.30 (m, 1H), 2.31-2.29 (m, 2H), 2.04-2.01 (m, 2H), 1.84 (s, 3H), 1.64-1.22 (m, 8H).
Reaction SMILES: [CH2:1]([NH:4][C:5]1[N:6]=[C:7](Cl)[C:8]2[CH:13]=[CH:12][N:11]([CH3:14])[C:9]=2[N:10]=1)[CH2:2][CH3:3].C(=O)([O-])[O-].[K+].[K+].[CH3:22][CH:23]([NH2:25])[CH3:24].O>C(O)CCC>[CH2:1]([NH:4][C:5]1[N:6]=[C:7]([NH:25][CH:23]([CH3:24])[CH3:22])[C:8]2[CH:13]=[CH:12][N:11]([CH3:14])[C:9]=2[N:10]=1)[CH2:2][CH3:3]
Reactant: CCCNc1nc(Cl)c2ccn(C)c2n1
Reactant: CC(C)N
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCCCO
Solvent: O
Product: CCCNc1nc(NC(C)C)c2ccn(C)c2n1
Temperature: 25 °C
Yield: 68.3 %

Procedure:
To a solution of 2-(n-propyl)amino-4-chloro-7-methyl-pyrrolo[2,3-d]pyrimidine (1.6 g, 7.1 mmol) in n-butanol (10 mL) was added potassium carbonate (4.9 g, 35.5 mmol), followed by propan-2-amine (632 mg, 10.7 mmol). The mixture was stirred in an autoclave equipped with a stirrer at 140° C. for 16 h. After cooling to room temperature, water was added (20 mL), and the mixture was extracted with EtOAc (3×50 mL). The combined organic layers were washed with water and then with a brine solution, and lastly dried over anhydrous Na2SO4. The volatiles were removed in vacuo and the residue was purified by flash column chromatography (PE/EtOAc=3/1) to yield 2-(n-propyl)amino-4-(i-propyl)amino-7-methyl-pyrrolo[2,3-d]pyrimidine (1.2 g, 75%) as a yellow solid. LCMS: (ESI) m/z=248 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][C:4]=1[CH3:12].[CH3:13][O:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[CH:20]([NH2:24])[CH2:19][CH2:18]2>>[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH:24][CH:20]2[C:21]3[C:17](=[CH:16][C:15]([O:14][CH3:13])=[CH:23][CH:22]=3)[CH2:18][CH2:19]2)=[O:9])=[CH:5][C:4]=1[CH3:12]
Reactant: COc1ccc2c(c1)CCC2N
Reactant: COc1ccc(C(=O)O)cc1C
Product: COc1ccc2c(c1)CCC2NC(=O)c1ccc(OC)c(C)c1

Procedure:
Prepared in a similar manner to example 4 using 4-methoxy-3-methylbenzoic acid and 5-methoxy-2,3-dihydro-1H-inden-1-amine (Example 121-2a) (47%). MS (M+Hs 312).
Reaction SMILES: [CH3:1][N:2]1[C:6]([CH2:7][C:8](O)=[S:9])=[N:5][N:4]=[N:3]1.S(Cl)([Cl:13])=O>C1C=CC=CC=1.CN(C)C=O>[CH3:1][N:2]1[C:6]([CH2:7][C:8]([Cl:13])=[S:9])=[N:5][N:4]=[N:3]1
Reactant: O=S(Cl)Cl
Reactant: Cn1nnnc1CC(O)=S
Solvent: c1ccccc1
Solvent: CN(C)C=O
Product: Cn1nnnc1CC(=S)Cl

Procedure:
To a suspension of (1-methyl-1H-tetrazol-5-yl)-thioacetic acid (10 g) in dried benzene (100 ml) were added a solution of thionyl chloride (10.2 g) in dried benzene (30 ml) and dimethylformamide (1 drop) in turn at room temperature, and the mixture was refluxed for 1 hour. After the reaction, the solvent was distilled off to give crystals of (1-methyl-1H-tetrazol-5-yl)thioacetyl chloride. To a solution of 3,4-dibenzyloxyphenethylamine (9.3 g) in a mixture of dried benzene (90 ml) and dried chloroform (10 ml) was firstly added triethylamine (3.66 g) and then was dropwise added over 20 minutes under stirring and ice cooling a solution of the above obtained (1-methyl-1H-tetrazol-5-yl)-thioacetyl chloride in a mixture of dried benzene (50 ml) and dried chloroform (5 ml). The mixture was stirred for 30 minutes at the same temperature and for 30 minutes at room temperature. The solvent was distilled off and the residue was dissolved in chloroform. The solution was in turn washed with 5% hydrochloric acid, water, dilute sodium bicarbonate aqueous solution and water and dried. The solvent was distilled off and the residue was crystallized from ether to give N-(3,4-dibenzyloxyphenethyl)-(1-methyl-1H-tetrazol-5-yl)-thioacetamide (10.7 g), mp 110° C.
Reaction SMILES: [Cl:1][C:2]1[CH:21]=[CH:20][C:5]([CH:6]([N:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[C:7]2[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[CH2:22]([CH:24]1[O:26][CH2:25]1)[Cl:23]>>[Cl:23][CH2:22][CH:24]([OH:26])[CH2:25][N:17]1[CH2:16][CH2:15][N:14]([CH:6]([C:7]2[CH:8]=[CH:9][C:10]([Cl:13])=[CH:11][CH:12]=2)[C:5]2[CH:20]=[CH:21][C:2]([Cl:1])=[CH:3][CH:4]=2)[CH2:19][CH2:18]1
Reactant: Clc1ccc(C(c2ccc(Cl)cc2)N2CCNCC2)cc1
Reactant: ClCC1CO1
Product: OC(CCl)CN1CCN(C(c2ccc(Cl)cc2)c2ccc(Cl)cc2)CC1

Procedure:
4,4'-Dichlorobenzhydrylpiperazine ((6.0 g, 18.7 mmol) was reacted as above with epichlorohydrin to give the title compound as an amber oil, 3.67 g (49.8%). 100 MHz 1H NMR (CDCl ) δ: 7.3 (s, 8H), 4.2 (s, 1H), 3.9 (m, 1H), 3.6 (d, 2H, J=10 Hz), 2.9 (m, 2H), 2.7-2.4 (m, 10H).
Reaction SMILES: [O:1]=[C:2]1[CH:7]=[CH:6][C:5]2[C:8](OS(C(F)(F)F)(=O)=O)=[CH:9][CH:10]=[CH:11][C:4]=2[O:3]1.[O:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]1[O:26][CH2:27][CH2:28][CH2:29][CH2:30][C:31]#[CH:32].C(N(CC)CC)C.CN(C)C=O>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CCOCC.O>[O:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]1[O:26][CH2:27][CH2:28][CH2:29][CH2:30][C:31]#[C:32][C:8]1[C:5]2[CH:6]=[CH:7][C:2](=[O:1])[O:3][C:4]=2[CH:11]=[CH:10][CH:9]=1
Reactant: O=c1ccc2c(OS(=O)(=O)C(F)(F)F)cccc2o1
Reactant: C#CCCCCOC1CCCCO1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CCN(CC)CC
Solvent: CCOCC
Solvent: O
Product: O=c1ccc2c(C#CCCCCOC3CCCCO3)cccc2o1
Temperature: 100 °C
Yield: 66.8 %

Procedure:
A mixture of 1.47 g (5 mmol) of trifluoromethanesulfonic acid 2-oxo-2H-1-benzopyran-5-yl ester, 1.0 g (5.5 mmol) of rac-6-[(tetrahydro-2H-pyran-2-yl)oxy]-1-hexyne, 75 mg of cuprous iodide, 0.3 g (0.428 mmol) of dichlorobis(triphenylphosphine)palladium (II), 7.5 mL of triethylamine, and 35 mL of dry N,N-dimethylformamide was stirred and heated at 100° C. for 24 hr. The reaction mixture was cooled, poured into water, and worked-up with ether in the usual manner. The dark-brown, oily residue was flash chromatographed on silica gel. Elution with 2:1 hexane-ethyl acetate gave 1.09 g (67%) of rac-5-[6-[(tetrahydro-2H-pyran-2-yl)oxy]-1-hexynyl]-2H-1-benzopyran-2-one as an orange oil.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:14]([C:18](O)=[O:19])=[CH:13][CH:12]=[CH:11][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:21]([O:23][C:24]([C:26]1([NH2:35])[CH2:34][C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH2:27]1)=[O:25])[CH3:22].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][C:14]=2[C:18](=[O:19])[NH:35][C:26]2([C:24]([O:23][CH2:21][CH3:22])=[O:25])[CH2:34][C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH2:27]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCc2c(cccc2C(=O)O)C1
Reactant: CCOC(=O)C1(N)Cc2ccccc2C1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)C1(NC(=O)c2cccc3c2CCN(C(=O)OC(C)(C)C)C3)Cc2ccccc2C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 30.5 %

Procedure:
To a solution of 3,4-dihydro-1H-isoquinoline-2,5-dicarboxylic acid 2-tert-butyl ester (2 g, 7.2 mmol), 2-amino-indan-2-carboxylic acid ethyl ester (1.5 g, 7.2 mmol), HATU (3.27 g, 8.6 mmol) in anhydrous DMF (20 mL) is added DIPEA (1.42 mL, 8.6 mmol). The resulting solution is stirred at RT overnight. After the removal of DMF in vacuo, the residue is dissolved in EtOAc (150 mL) and washed with water (1×20 mL) and brine (2×20 mL). The organic layer is dried over anhydrous Na2SO4 and concentrated in vacuo. The residue is purified by HPLC to give a pure product (71) as white solid (1.02 g, 30%).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)[CH:5]=[C:4]([CH:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)[N:3]=1.C([O:30][C:31]1[CH:32]=[C:33]([CH:37]=[CH:38][C:39]=1[O:40]CC1C=CC=CC=1)[C:34](O)=[O:35])C1C=CC=CC=1.ON1C2C=CC=CC=2N=N1>ClCCl>[NH2:1][C:2]1[N:3]=[C:4]([CH:17]2[CH2:22][CH2:21][N:20]([C:34](=[O:35])[C:33]3[CH:37]=[CH:38][C:39]([OH:40])=[C:31]([OH:30])[CH:32]=3)[CH2:19][CH2:18]2)[CH:5]=[C:6]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=2)[N:7]=1
Reactant: COc1ccc(Cc2cc(C3CCNCC3)nc(N)n2)cc1
Reactant: O=C(O)c1ccc(OCc2ccccc2)c(OCc2ccccc2)c1
Agent: On1nnc2ccccc21
Solvent: ClCCl
Product: COc1ccc(Cc2cc(C3CCN(C(=O)c4ccc(O)c(O)c4)CC3)nc(N)n2)cc1
Reaction time: 0.5 h
Yield: 203.3 %

Procedure:
To a solution of 2-amino-4-(4-methoxyphenylmethyl)-6-(4-piperidinyl)pyrimidine (160 mg, 0.54 mmol), 3,4-dibenzyloxybenzoic acid (179 mg, 0.54 mmol) and 1-hydroxybenzotriazole (72 mg, 0.54 mmol) in dichioromethane (150 ml) were added 1-ethyl-3-(N, N'-dimethylaminopropyl)carbodiimide hydrochloride (103 mg, 0.54 mmol) at room temperature under nitrogen atmosphere. After stirring for about 30 minutes, the mixture was washed successively with saturated sodium hydrogen carbonate solution and brine. The organic layer was dried over anhydrous sodium sulfate and then evaporated. The residue was purified by column chromatography (chloroform:methanol=99:1) to give the titled compound (477 mg).
Reaction SMILES: C([O:3][C:4](=[O:26])[CH:5]([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH2:6][NH:7][C:8]1[S:9][CH:10]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:12]=1)C.[OH-].[K+].OS([O-])(=O)=O.[K+]>CCO.O>[CH2:19]([CH:5]([CH2:6][NH:7][C:8]1[S:9][CH:10]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:12]=1)[C:4]([OH:26])=[O:3])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: CCOC(=O)C(CNc1nc(-c2ccccc2)cs1)Cc1ccccc1
Agent: O=S(=O)([O-])O
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=C(O)C(CNc1nc(-c2ccccc2)cs1)Cc1ccccc1
Reaction time: 5 h

Procedure:
To a solution of 2-Benzyl-3-(4-phenyl-thiazol-2-ylamino)-propionic ethyl ester (22r) (0.028 mmol, 10 mg) in EtOH (2 mL) and water (200 μL) is added KOH 1N solution (224 μL, 8 eq.). After 5 hours, the solution is neutralized with KHSO4 1N solution and lyophilized before purification.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[C:8]([N+:10]([O-:12])=[O:11])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].N1C=CC=CC=1.[F:19][C:20]1[CH:28]=[CH:27][C:23]([C:24](Cl)=[O:25])=[CH:22][CH:21]=1>O1CCCC1.C(OCC)(=O)C.C(=O)([O-])O.[Na+]>[C:4]([C:3]1[CH:6]=[CH:7][C:8]([N+:10]([O-:12])=[O:11])=[CH:9][C:2]=1[NH:1][C:24](=[O:25])[C:23]1[CH:27]=[CH:28][C:20]([F:19])=[CH:21][CH:22]=1)#[N:5]
Reactant: N#Cc1ccc([N+](=O)[O-])cc1N
Reactant: O=C(Cl)c1ccc(F)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: N#Cc1ccc([N+](=O)[O-])cc1NC(=O)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 31.5 %

Procedure:
To a mixture of 2-amino-4-nitro-benzonitrile (3.3 g, 20.23 mmol) and pyridine (4.88 ml, 60.68 mmol) in anhydrous tetrahydrofuran (30 ml) under an atmosphere of nitrogen was added 4-fluorobenzoyl chloride (2.67 ml, 22.25 mmol). The reaction mixture was stirred at ambient temperature for 1 hour. Then more 4-fluorobenzoyl chloride (2.67 ml, 22.25 mmol) was added to the mixture. The reaction mixture was stirred at 50° C. for 1 hour. The reaction mixture was diluted with ethyl acetate and aqueous sodium hydrogen carbonate (saturated). The phases were separated and the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated. The residue was dissolved in methanol (200 ml) and potassium carbonate (5.1 g) was added. The reaction mixture was stirred for 16 hours at ambient temperature. The reaction mixture was diluted with ethyl acetate and aqueous sodium hydrogen carbonate (saturated). The phases were separated and the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: cyclohexane/tetrahydrofuran 10:1) to give N-(2-cyano-5-nitro-phenyl)-4-fluoro-benzamide (1.82 g, 32% yield). 1H-NMR (DMSO-d6, 400 MHz): 11.02 (s, 1H), 8.48 (s, 1H), 8.20 (s, 2H), 8.11 (m, 2H), 7.45 (m, 2H) ppm.
Reaction SMILES: Cl.[CH2:2]([N:9]1[CH:13]=[C:12]([C:14]([NH:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24](=[NH:26])[NH2:25])=[CH:20][CH:19]=2)=[O:15])[CH:11]=[N:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(=O)([O-])[O-].[K+].[K+].Cl[C:34]([O:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])=[O:35]>O.O1CCCC1>[NH2:26]/[C:24](=[N:25]\[C:34](=[O:35])[O:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])/[C:21]1[CH:20]=[CH:19][C:18]([CH2:17][NH:16][C:14]([C:12]2[CH:11]=[N:10][N:9]([CH2:2][C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=3)[CH:13]=2)=[O:15])=[CH:23][CH:22]=1
Reactant: CCCCCCOC(=O)Cl
Reactant: N=C(N)c1ccc(CNC(=O)c2cnn(Cc3ccccc3)c2)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: CCCCCCOC(=O)/N=C(\N)c1ccc(CNC(=O)c2cnn(Cc3ccccc3)c2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 90 %

Procedure:
30 mg of 1-benzyl-N-[(4-carbamimidoylphenyl)methyl]pyrazole-4-carboxamide hydrochloride and 35 mg of potassium carbonate were dissolved in 0.4 ml of water and 2 ml of tetrahydrofuran. The mixture was stirred at room temperature, and 0.013 ml of n-hexyl chloroformate (Sigma-Aldrich) added. Stirring was continued for 1 h, following which the organic layer was removed, and dried in vacuo to obtain the synthetic target (>90% yield). The mass of the compound was verified using LC/MS/MS.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[C:4](I)[CH:3]=1.[CH3:10][NH:11][S:12]([C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=1)(=[O:14])=[O:13].C([O-])([O-])=O.[Na+].[Na+].[O-]S([O-])(=O)=O.[Na+].[Na+]>O1CCOCC1.CCOC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[C:4]([C:18]2[CH:17]=[CH:16][C:15]([S:12]([NH:11][CH3:10])(=[O:13])=[O:14])=[CH:20][CH:19]=2)[CH:3]=1
Reactant: CNS(=O)(=O)c1ccc(B(O)O)cc1
Reactant: Fc1ccc(Br)cc1I
Agent: O=C([O-])[O-]
Agent: O=S(=O)([O-])[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: CNS(=O)(=O)c1ccc(-c2cc(Br)ccc2F)cc1
Temperature: 120 °C
Yield: 67 %

Procedure:
To a solution of 4-bromo-1-fluoro-2-iodobenzene (207 mg, 0.69 mmol) in anhydrous dioxane (3.4 mL) was added [4-(methylsulfamoyl)phenyl]boronic acid (148 mg, 0.69 mmol) and aqueous Na2CO3 solution (2M, 1.03 mL, 2.06 mmol). A stream of nitrogen gas was bubbled through the reaction mixture for 6 minutes. Tetrakistriphenylphosphine palladium(0) (24 mg, 0.021 mmol) was added and the mixture was heated under microwave irradiation at 120° C. for 12 minutes. The reaction mixture was cooled, diluted with EtOAc, treated with anhydrous Na2SO4 and filtered, washing the solids with EtOAc until the compound had completely eluted. The filtrate was evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with heptane:EtOAc 100:0 to 60:40 to afford the title compound as clear, colorless residue in 67% yield, 159 mg.
Reaction SMILES: [CH3:1][C:2]([Si:5]([C:28]1C=CC=CC=1)([C:22]1C=CC=CC=1)[O:6][CH2:7][CH:8]([NH:13][C:14](=[O:21])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[CH:9](O)[CH2:10]C)([CH3:4])[CH3:3].[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=[O:35].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>CN(C)C=O.O>[CH3:4][C:2]([Si:5]([CH3:22])([CH3:28])[O:6][CH2:7][C@@H:8]([NH:13][C:14](=[O:21])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[CH2:9][CH:10]=[O:35])([CH3:1])[CH3:3]
Reactant: CCCCCCC(=O)NC(CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)C(O)CC
Reactant: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: c1cc[nH+]cc1
Solvent: CN(C)C=O
Solvent: O
Product: CCCCCCC(=O)N[C@@H](CC=O)CO[Si](C)(C)C(C)(C)C
Reaction time: 18 h
Yield: 81.8 %

Procedure:
A mixture of (10c), (2.30 g, 6.94 mmol) and pyridinium dichromate (10.62 g, 28.2 mmol) in 20 mL of N,N-dimethylformamide is stirred under argon for 18 h. The reaction mixture is diluted with 100 mL of water and extracted with ethyl acetate (3×40 mL). The organic layer is separated, washed with water and brine, dried and evaporated to give 1.87 g of a residual brown liquid. The liquid is purified by chromatography using 1:6 ethyl acetate/hexane to give 997 mg of the desired product as an oil. NMR δ0.83 (S, 9H), 1.61 (m, 2H), 2.22 (t, 2H), 2.23 (s, 3H), 3.82 (dd, 1H), 4.09 (dd, 1H), 4.57 (m, 1H), 6.42 (brd, 1H); MS (FAB) m/z 330 (M+H calc'd for C17H36NO3Si 330).
Reaction SMILES: C(N(CC)CC)C.[C:8]([C@@H:12]1[CH2:17][CH2:16][C@H:15]([NH2:18])[CH2:14][CH2:13]1)([CH3:11])([CH3:10])[CH3:9].[CH2:19]([C:21]1[C:26]([Cl:27])=[C:25](Cl)[N:24]2[N:29]=[CH:30][N:31]=[C:23]2[N:22]=1)[CH3:20]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[C:8]([C@@H:12]1[CH2:13][CH2:14][C@H:15]([NH:18][C:25]2[N:24]3[N:29]=[CH:30][N:31]=[C:23]3[N:22]=[C:21]([CH2:19][CH3:20])[C:26]=2[Cl:27])[CH2:16][CH2:17]1)([CH3:11])([CH3:9])[CH3:10]
Reactant: CCc1nc2ncnn2c(Cl)c1Cl
Reactant: CC(C)(C)[C@H]1CC[C@@H](N)CC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [I-]
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CCc1nc2ncnn2c(N[C@H]2CC[C@@H](C(C)(C)C)CC2)c1Cl

Procedure:
0.280 g (2.76 mmol) Triethylamine, a spatula tip of tetrabutylammonium iodide and 0.393 g (2.53 mmol) of cis-4-tert-butylcyclohexylamine were added successively to a solution of 0.500 g (2.3 mmol) of 5-ethyl-6,7-dichloro-[1,2,4]triazolo[1,5-a]pyrimidine in 10 ml of toluene under stirring. The reaction mixture was heated at reflux for 5 hours and then stirred for another 12 hours at room temperature. The solvent was evaporated under reduced pressure and dichloromethane was added to the resulting residue. The resulting reaction mixture was washed with 2N hydrochloric acid and water. The organic phase was separated, dried and the solvent was evaporated under reduced pressure. Treatment of the resulting residue with hexane yielded 0.420 g (1.2 mmol, 52% of theory) of the title compound having a melting point of 120-122° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]([OH:38])([CH2:32]OS(C)(=O)=O)[C@H:10]([N:12]1[C:16](=[O:17])[N:15]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]([F:31])([F:30])[CH:27]([F:29])[F:28])=[CH:20][CH:19]=2)[CH:14]=[N:13]1)[CH3:11].[NH:39]1[CH:43]=[N:42][CH:41]=[N:40]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]([OH:38])([CH2:32][N:39]1[CH:43]=[N:42][CH:41]=[N:40]1)[C@H:10]([N:12]1[C:16](=[O:17])[N:15]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]([F:31])([F:30])[CH:27]([F:28])[F:29])=[CH:20][CH:19]=2)[CH:14]=[N:13]1)[CH3:11]
Reactant: c1nc[nH]n1
Reactant: C[C@@H](n1ncn(-c2ccc(OCC(F)(F)C(F)F)cc2)c1=O)[C@](O)(COS(C)(=O)=O)c1ccc(F)cc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: C[C@@H](n1ncn(-c2ccc(OCC(F)(F)C(F)F)cc2)c1=O)[C@](O)(Cn1cncn1)c1ccc(F)cc1F
Temperature: 90 °C
Yield: 76.6 %

Procedure:
2-[(1R,2S)-2-(2,4-Difluorophenyl)-2-hydroxy-3-methanesulfonyloxy-1-methylpropyl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-3(2H,4H)-1,2,4-triazolone (10 g) was dissolved in 180 ml of dimethylformamide, to which 5.7 g of 1H-1,2,4-triazole and 23.2 g of potassium carbonate were added. The mixture was heated at 90° C. for 5 hours. The reaction solution was concentrated under reduced pressure to ca. 100 ml and diluted with a mixture of 400 ml of ethyl acetate and 200 ml of diisopropyl ether. The mixture was washed with 100 ml of water, 1N-hydrochloric acid (100 ml×2) and 100 ml of an aqueous solution of sodium chloride successively. The organic layer was dried over magnesium sulfate. After the solvent was distilled off under reduced pressure, the residue was purified by silica gel chromatography (silica gel: 70 g, eluent; hexane:ethyl acetate=3:4 to ethyl acetate). The desired fraction was concentrated and the residue was recrystallized from a mixture of 10 ml of ethyl acetate and 80 ml of diisopropyl ether to give 7.3 g of 2-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-3(2H,4H)-1,2,4-triazolone (yield: 80%) as a colorless powdery crystals.
Reaction SMILES: [CH2:1]([NH2:4])[CH2:2][NH2:3].[N:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH:11]=O.[BH4-].[Na+]>CO>[N:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:2]=1[CH2:1][NH:4][CH:6]([NH:5][CH2:11][C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][N:5]=1)[CH3:11]
Reactant: NCCN
Reactant: O=Cc1ccccn1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CC(NCc1ccccn1)NCc1ccccn1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
This ligand was prepared according to a modified procedure described by Bernal et al in J. Chem. Soc., Dalton Trans, 22, 3667 (1995). First N,N′-bis(pyridin-2ylmethyl)-ethanediamine (bispicen) was synthesised by the following procedure. Ethylenediamine (26 ml, 0.38 mol) was dissolved in 200 ml dry methanol. To this mixture 74 ml (0.76 mol) pyridincarboxaldehyde was added. The mixture was refluxed for 2 h, after which the mixture was left to cool to RT and in small portions 40 g of NaBH4 was added. The mixture was subsequently stirred for 16 h at RT. The methanol was evaporated and 500 ml of water was added. The aqueous mixture was extracted with three portions of dichloromethane (100 ml) and the dichloromethane solution was dried over sodium sulphate, filtered off and the solvent was removed. The dark oil containing N,N′-bis(pyridin-2ylmethyl)-ethanediamine (73.7 g; 81%) was analysed by NMR and used without further purification. 1H-nmr (CDCl3): δ2.20 (br, NH); 2.78 (s, 4H); 3.85 (s, 4H); 7.00-7.40 (m, 4H); 7.58 (m, 2H); 8.45 (m, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH2:9])=[CH:5][CH:4]=1.[F:10][C:11]1[CH:16]=[CH:15][C:14]([S:17](Cl)(=[O:19])=[O:18])=[CH:13][C:12]=1[N+:21]([O-:23])=[O:22]>CO>[F:10][C:11]1[CH:16]=[CH:15][C:14]([S:17]([NH:9][C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)(=[O:19])=[O:18])=[CH:13][C:12]=1[N+:21]([O-:23])=[O:22]
Reactant: O=[N+]([O-])c1cc(S(=O)(=O)Cl)ccc1F
Reactant: COc1ccc(N)cc1
Solvent: CO
Product: COc1ccc(NS(=O)(=O)c2ccc(F)c([N+](=O)[O-])c2)cc1
Reaction time: 0.25 h
Yield: 59.8 %

Procedure:
p-Anisidine (760 mg, 6.18 mmol) was added to a solution of 4-fluoro-3-nitrophenylsulfonyl chloride (740 mg, 3.09 mmol; Example A) in MeOH (10 ml) at ambient temperature. After stining at room temperature for 15 min, the reaction mixture was concentrated under reduced pressure and the residue was taken up in ethyl acetate and filtered through a pad of silica gel. Concentration of the filtrate, followed by chromatography, provided 603 mg (60% yield) of the title compound. 1H-NMR (CDCl3): δ 8.42 (1H, dd, J=2.3, 6.8 Hz), 7.88 (1H, ddd, J=2.4, 4.0, 8.8 Hz), 7.33 (1H, dd, J=8.8, 9.9 Hz), 6.98 (2H, m), 6.81 (2H, m), 6.45 (1H, s), 3.77 (3H, s). MS (EI): 326 (11, M+), 122 (100). Anal. Calcd. for C13H11FN2O5S: C, 47.85; H, 3.40; N, 8.59; S, 9.83. Found: C, 47.68; H, 3.44; N, 8.54; S, 9.88.