Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:8]1)=[O:6].C1(C)C=CC=CC=1.CO>C1COCC1.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:5]([OH:6])[C@@H:7]2[CH2:12][CH2:11][CH2:10][N:9]([C:13]([O:15][C:16]([CH3:18])([CH3:17])[CH3:19])=[O:14])[CH2:8]2)[CH:20]=[CH:21][CH:22]=1
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H](C(=O)c2cccc(Cl)c2)C1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N1CCC[C@@H]([C@@H](O)c2cccc(Cl)c2)C1
Temperature: -15 °C
Reaction time: 1 h
Yield: 11.2 %

Procedure:
To a solution of (R)-tert-butyl 3-(3-chlorobenzoyl)piperidine-1-carboxylate (178 g, 0.55 mol) in anhydrous THF (600 mL) at −15° C. under nitrogen was added dropwise a solution of 1 M R-CBS-oxazaborolidine in toluene (82 mL, 82 mmol, 0.15 eq). After stirring for 1 hr at −15° C., a solution of 10 M BH3 in THF (60 mL, 0.60 mol, 1.1 eq) was added dropwise. After addition, the reaction mixture was stirred for 2 hr at −15° C. Methanol (400 mL) was added dropwise carefully at −15° C. The solvent was removed under reduced pressure, the residue was purified by column chromatography on silica gel eluting with AcOEt/hexane (1:30→1:15) to provide the light yellow oil (95 g, HPLC purity≧70%, isomer ratio≧3:1). The mixture was dissolved in EtOAc till the alcohol was just dissolved (about 5 mL/1 g), the solvent was removed on the rotary evaporator until a few crystals appeared. The solution was cooled to rt slowly and stood for 1-2 hr. To the above solution was added hexane (about 300 mL) and then filtered, the crystals were washed with cool hexane and re-crystallized from AcOEt-hexane twice to afford the pure isomer (R)-tert-butyl 3-((R)-(3-chlorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (20 g, ee≧99%).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]([CH3:17])=[CH:7][C:8]1[CH:16]=[CH:15][CH:14]=[CH:13][C:9]=1[C:10]([OH:12])=O)=[O:5])[CH3:2].C(N(CC)CC)C.F[B-](F)(F)F.C(C(=NOC(N(C)C)=[N+](C)C)C(OCC)=O)#N.[CH2:47]([NH2:51])[CH:48]([CH3:50])[CH3:49]>CN(C)C=O>[CH2:47]([NH:51][C:10]([C:9]1[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=1[CH:7]=[C:6]([CH3:17])[C:4]([O:3][CH2:1][CH3:2])=[O:5])=[O:12])[CH:48]([CH3:50])[CH3:49]
Reactant: CCOC(=O)C(C)=Cc1ccccc1C(=O)O
Reactant: CC(C)CN
Agent: CCOC(=O)C(C#N)=NOC(N(C)C)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCOC(=O)C(C)=Cc1ccccc1C(=O)NCC(C)C
Yield: 79.5 %

Procedure:
Ethyl 3-(2-isobutylcarbamoylphenyl)-2-methylacrylate is prepared as described in Example 30, starting with 1.17 g (5.0 mmol) of 2-(2-ethoxycarbonylpropen-1-yl)benzoic acid in 10 cm3 of dimethylformamide, a solution of 0.69 cm3 (5.0 mmol) of triethylamine, 1.64 g (5.0 mmol) of O-[(cyano(ethoxycarbonyl)methylene)amino]-1,1,3,3-tetramethyluronium tetrafluoroborate (“TOTU”) in 6 cm3 of dimethylformamide and a second solution consisting of 366 mg (5.0 mmol) of isobutylamine, 0.69 cm3 (5.0 mmol) of triethylamine in 10 cm3 of dimethylformamide. 1.15 g of ethyl 3-(2-isobutylcarbamoylphenyl)-2-methylacrylate are thus obtained in the form of a yellowish oil, which can be reacted in the following step without further purification.
Reaction SMILES: CC([O-])(C)C.[K+].CS(O[CH2:12][C:13]1[N:14]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[CH:17][CH:16]=2)(=O)=O.[O:29]1[CH2:34][CH2:33][CH:32]([NH:35][C:36]2[N:41]=[C:40]([C:42]3[CH:47]=[CH:46][NH:45][C:44](=[O:48])[CH:43]=3)[CH:39]=[CH:38][N:37]=2)[CH2:31][CH2:30]1.O>[N+](CCCC)(CCCC)(CCCC)CCCC.[I-].C1COCC1.ClCCl.CC#N>[O:48]=[C:44]1[CH:43]=[C:42]([C:40]2[CH:39]=[CH:38][N:37]=[C:36]([NH:35][CH:32]3[CH2:33][CH2:34][O:29][CH2:30][CH2:31]3)[N:41]=2)[CH:47]=[CH:46][N:45]1[CH2:12][C:13]1[N:14]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[CH:17][CH:16]=2
Reactant: CC(C)(C)OC(=O)n1c(COS(C)(=O)=O)cc2ccccc21
Reactant: O=c1cc(-c2ccnc(NC3CCOCC3)n2)cc[nH]1
Agent: CC(C)(C)[O-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [I-]
Solvent: O
Solvent: CC#N
Solvent: ClCCl
Product: CC(C)(C)OC(=O)n1c(Cn2ccc(-c3ccnc(NC4CCOCC4)n3)cc2=O)cc2ccccc21
Temperature: 70 °C
Reaction time: 2 h
Yield: 25.9 %

Procedure:
KOt-Bu (224 mg, 2 mmol) and n-Bu4NI (37 mg, 0.1 mmol) were added to a mixture of tert-butyl 2-((methylsulfonyloxy)methyl)-1H-indole-1-carboxylate (350 mg, 1.07 mmol) and 4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (272 mg, 1 mmol) in anhydrous THF (15 mL). The resulting mixture was stirred at 70° C. under microwave irradiation for 2 hours. LC-MS showed the tert-butyl 2-(((methylsulfonyl)oxy)methyl)-1H-indole-1-carboxylate had disappeared. The reaction mixture was treated with water (20 mL) and diluted with dichloromethane. After removal of the insolubles by filtration, the filtrate was extracted with dichloromethane. The combined organic phase was dried with Na2SO4 and concentrated. The residue was purified with Combiflash (A: H2O including 0.5% NH3HCO3, B: CH3CN) to afford tert-butyl 2-((2-oxo-4-(2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4-yl)pyridin-1(2H)-yl)methyl)-1H-indole-1-carboxylate (130 mg, 26% yield).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:10](Cl)=[N:11][OH:12])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[Cl:14][C:15]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:16]=1[CH:17]=[CH2:18].C(N(CC)CC)C>C1COCC1>[Cl:14][C:15]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:16]=1[CH:17]1[O:12][N:11]=[C:10]([C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[CH2:18]1
Reactant: O=[N+]([O-])c1cccc(C(Cl)=NO)c1
Reactant: C=Cc1c(Cl)cccc1Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=[N+]([O-])c1cccc(C2=NOC(c3c(Cl)cccc3Cl)C2)c1

Procedure:
3-Nitro-N-hydroxybenzenecarboximidoyl chloride (1.16 g, 5.78 mmol) and 2,6-dichlorostyrene (1.0 g, 5.78 mmol) were dissolved in anhydrous THF (20 mL) and triethylamine (1.21 mL, 8.67 mmol). Upon addition of triethylamine a while solid formed. After 3 h this solid was collected by filtration under reduced pressure to provide the title compound as a white solid.
Reaction SMILES: [CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[C:5]=2[C:15]([OH:17])=O)[CH2:3][CH2:2]1.Cl.[CH3:19][NH:20][O:21][CH3:22].CN1CCOCC1.CN(C)CCCN=C=NCC.Cl>CN(C)C1C=CN=CC=1.ClCCl.CN(C=O)C>[CH3:22][O:21][N:20]([CH3:19])[C:15]([C:5]1[C:6]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[N:7][O:8][C:4]=1[CH:1]1[CH2:2][CH2:3]1)=[O:17]
Reactant: O=C(O)c1c(-c2ccccc2)noc1C1CC1
Reactant: CNOC
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Solvent: CN1CCOCC1
Solvent: CN(C)C=O
Product: CON(C)C(=O)c1c(-c2ccccc2)noc1C1CC1
Temperature: 0 °C
Reaction time: 2 h
Yield: 92.5 %

Procedure:
A mixture of 5-cyclopropyl-3-phenyl-isoxazole-4-carboxylic acid (3.72 g, 16 mmol), N,O-dimethylhydroxylamine hydrochloride (2.53 g, 26 mmol), N-methylmorpholine (2.85 mL, 26 mmol) and 4-dimethylaminopyridine (198 mg, 2 mmol) in dichloromethane (50 mL) and DMF (10 mL) was cooled to 0° C. Then 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (3.73 g, 19 mmol) was added and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was poured into hydrochloric acid (1 N) and extracted with ethyl acetate. The combined organic layers were then washed with a saturated solution of sodium hydrogen carbonate, brine and then dried over sodium sulphate and evaporated to leave a light yellow oil. Purification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 50:50) afforded the title compound (4.03 g, 91%) which was obtained as a colourles oil. MS: m/e=273.0 [M+H]+.
Reaction SMILES: [F:1][C:2]([F:19])([F:18])[C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.C1C=CC2N(O)N=NC=2C=1.O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:55][C:56]1[N:61]=[C:60]([C:62](O)=[O:63])[CH:59]=[CH:58][CH:57]=1.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl>[CH3:55][C:56]1[N:61]=[C:60]([C:62]([N:15]2[CH2:16][CH2:17][N:12]([S:9]([C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:18])[F:19])=[CH:8][CH:7]=3)(=[O:10])=[O:11])[CH2:13][CH2:14]2)=[O:63])[CH:59]=[CH:58][CH:57]=1
Reactant: O=S(=O)(c1ccc(C(F)(F)F)cc1)N1CCNCC1
Reactant: Cc1cccc(C(=O)O)n1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: Cc1cccc(C(=O)N2CCN(S(=O)(=O)c3ccc(C(F)(F)F)cc3)CC2)n1
Temperature: 25 °C
Reaction time: 2 h
Yield: 70.4 %

Procedure:
To a solution of 1-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazine (Description 1) (100 mg, 0.340 mmol) in DMF (5 ml) was added HOBT.H2O (52.0 mg, 0.340 mmol), HBTU (129 mg, 0.340 mmol), 6-methyl-2-pyridinecarboxylic acid (46.6 mg, 0.340 mmol) and DIPEA (0.178 ml, 1.019 mmol). The reaction mixture was stirred for 2 hours at room temperature. Reaction mixture was transferred to a 100 ml round bottom flask and was reduced to dryness in vacuo. The residue was dissolved in DCM (50 ml) and transferred to a separating funnel then was washed with saturated aq. NaHCO3 solution (5 ml), twice. The organic layer was collected and dried with dried magnesium sulphate. The solid was removed by filtration and the filtrate collected in a 250 ml round bottom flask and concentrated to dryness in vacuo. The residue was then dissolved in 1.8 ml 1:1 MeCN/DMSO and purified by MDAP in 2 batches. The fractions containing desired product were combined in a 250 ml round bottom flask and concentrated in vacuo to yield the title compound (99 mg).
Reaction SMILES: [OH-].[Na+:2].[OH:3][C:4]1[CH:9]=[CH:8][C:7]([S:10]([OH:13])(=[O:12])=[O:11])=[CH:6][C:5]=1[I:14].[CH2:15](Br)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.O.S(=O)(=O)(O)O>C(O)(C)C>[CH2:15]([O:3][C:4]1[CH:9]=[CH:8][C:7]([S:10]([O-:13])(=[O:11])=[O:12])=[CH:6][C:5]=1[I:14])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[Na+:2]
Reactant: O=S(=O)(O)c1ccc(O)c(I)c1
Reactant: BrCc1ccccc1
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)O
Solvent: O
Product: O=S(=O)([O-])c1ccc(OCc2ccccc2)c(I)c1
Temperature: 84 °C
Reaction time: 0.21 h

Procedure:
Sodium hydroxide (pellets, 110 g, 2.75 mol, 3.00 eq) was added portionwise to the vigorously stirring aqueous solution of the 4-hydroxy-3-iodo-benzenesulfonic acid. After addition was complete, 10-15 min., isopropyl alcohol (150 mL) was added to the resulting white suspension. The dropping-funnel was charged with benzyl bromide (Aldrich; 164.9 g, 0.964 mol, 1.05 eq.) and added to the reaction mixture over a period of approx. 5 mins. and the reaction mixture was heated to 80°≦Tint≦84° C. After approx. 25 min. it was determined that the reaction was not proceeding further and therefore additional sodium hydroxide (3.67 g, 91.8 mmol, 0.1 eq.) and then benzyl bromide (15.7 g, 91.8 mmol, 0.1 eq.) were added to the reaction mixture to give a homogenous solution. After 70 min. from the original benzyl bromide addition, the heating was stopped and the reaction was allowed to cool slowly in the oil-bath with stirring. At 7.5 h, the reaction mixture appeared as a suspension of fine-reflective precipitate in brown liquid. The reaction mixture was acidified with 3:1 water-sulfuric acid from about pH 13 to between pH 7.5 and 8 (approx. 70 mL is required). The reaction mixture was then cooled gradually to about 5° C. and stirred at that temperature for ˜1 h. The waxy white plaques were collected by filtration, washed with dichloromethane and dried under high vaccum (lyophilizer, 100-200 mTorr) for ˜24 h to give sodium 4-benzyloxy-3-iodo-benzenesulfonate as a brilliant white, crystalline solid, (267.7 g, 71%).
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]([NH2:6])=[O:5].C(=O)([O-])[O-].[Na+].[Na+].C(N1[C:22](=[O:23])[C:21]2=[CH:24][CH:25]=[CH:26][CH:27]=[C:20]2[C:19]1=[O:28])(OCC)=O>O.C(O)C>[CH:25]1[CH:24]=[C:21]2[C:22]([N:2]([CH2:3][C:4]([NH2:6])=[O:5])[C:19](=[O:28])[C:20]2=[CH:27][CH:26]=1)=[O:23]
Reactant: CCOC(=O)N1C(=O)c2ccccc2C1=O
Reactant: NCC(N)=O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: NC(=O)CN1C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 65.2 %

Procedure:
To a stirred solution of glycinamide hydrochloride (2.20 g, 20.0 mmoL) and sodium carbonate (2.54 g, 24 mmoL) in 25 mL of water is added N-carbethoxyphthalimide (4.38 g, 20.0 mmoL). The resulting suspension is stirred for 1.5 hour and then filtered to afford 3.22 g (79%) of the crude product as a white powder. The crude product is slurried in 200 mL of refluxing ethanol. The resulting suspension after cooling to room temperature is filtered and the solid dried in vacuo (60° C., <1 mm) to afford 2.65 g (65%) of N-phthaloylglycinamide as a white powder: mp 199°-201° C.; 1H NMR (DMSO-d6) δ 8.00-7.8 (m, 4 H, Ar), 7.70 (br s, 1 H, CONH2), 7.26 (br s, 1 H, CONH2), 4.16 (s, 2 H, CH2); 13C NMR (DMSO-d6) δ 167.8, 167.5, 134.4, 131.7, 123.1, 39.9. Anal. Calcd for C11H10N2O3. Theoretical: C, 60.55; H, 4.62; N, 12.84. Found: C, 60.49; H, 4.59; N, 12.82.
Reaction SMILES: [CH2:1]([O:19][CH2:20][CH2:21][CH2:22][OH:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[Br:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]Br.[OH-].[Na+]>[Cl-].C([N+](C)(C)C)CCCCCCCCCCCCCCC>[Br:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][O:23][CH2:22][CH2:21][CH2:20][O:19][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: BrCCCCCBr
Reactant: CCCCCCCCCCCCCCCCCCOCCCO
Agent: CCCCCCCCCCCCCCCC[N+](C)(C)C
Agent: [Cl-]
Agent: [Na+]
Product: CCCCCCCCCCCCCCCCCCOCCCOCCCCCBr

Procedure:
Employing 3-(octadecyloxy)propanol (5 g), 1,5-dibromopentane (10.8 g), cetyltrimethylammonium chloride (0.96 g) and a 50% aqueous solution of sodium hydroxide (12 g), a reaction and aftertreatment are conducted in the same manner as those in Reference Example 4 to obtain the above-titled compound as colorless wax (3.75 g).
Reaction SMILES: [N+:1]([C:4]1[CH:16]=[CH:15][C:7]([CH2:8][NH:9][S:10]([CH2:13][CH3:14])(=[O:12])=[O:11])=[CH:6][CH:5]=1)([O-])=O>CO.O1CCCC1.[Pd]>[NH2:1][C:4]1[CH:16]=[CH:15][C:7]([CH2:8][NH:9][S:10]([CH2:13][CH3:14])(=[O:12])=[O:11])=[CH:6][CH:5]=1
Reactant: CCS(=O)(=O)NCc1ccc([N+](=O)[O-])cc1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CO
Product: CCS(=O)(=O)NCc1ccc(N)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 74 %

Procedure:
N-(4-Nitrobenzyl)ethanesulfonamide (776 mg, 3.18 mmol) was dissolved in methanol and tetrahydrofuran (1:1, 35 mL). 10% Pd/C (264 mg, 3 equiv) was added to it. The resulting mixture was stirred at room temperature for overnight under H2. TLC showed complete consumption of starting material. The mixture was filtered through celite bed and the filterate was concentrated under reduced pressure. The crude was purified by column chromatography to give N-(4-aminobenzyl)ethanesulfonamide (504 mg, 74%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([CH:13]([CH2:17][CH3:18])[C:14]([OH:16])=[O:15])=[CH:8][CH:7]=[CH:6]2.S(Cl)(Cl)=O.O[N:24]1[C:28](=[O:29])[CH2:27][CH2:26][C:25]1=[O:30].N1C=CC=CC=1>C(Cl)Cl.C1(C)C=CC=CC=1.C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([CH:13]([CH2:17][CH3:18])[C:14]([O:16][CH:26]1[CH2:27][C:28](=[O:29])[NH:24][C:25]1=[O:30])=[O:15])=[CH:8][CH:7]=[CH:6]2
Reactant: O=C1CCC(=O)N1O
Reactant: CCC(C(=O)O)c1cccc2cc(OC)ccc12
Solvent: c1ccncc1
Solvent: ClCCl
Solvent: O=S(Cl)Cl
Product: CCC(C(=O)OC1CC(=O)NC1=O)c1cccc2cc(OC)ccc12
Reaction time: 8 h
Yield: 8.3 %

Procedure:
A mixture of 2-(6'methoxynaphthyl)butyric acid (0.519 g, 2.12 mmol) in 20 mL of dry methylene chloride was treated with 3.19 mL of a 2.0 thionyl chloride (6.37 mmol) solution and the resulting solution was allowed to stir overnight. The volatile solvents were removed under vacuum to give the crude acid chloride which was used without further purification. A portion of the acid chloride (139 mg, 0.53 mmol) in 10 mL of dry toluene was added to a stirred solution of N-hydroxysuccinimide (61 mg, 0.53 mmol) and pyridine (42 mg, 0.53 mmol) in 10 mL of dry THF. After stirring overnight, the precipitated pyridine hydrochloride was filtered off and the filtrate concentrated under vacuum. The residue was chromotographed on silica gel (CHCl3 /MeOH) to afford 15 mg of the product as a white solid. Yield 8%; 1H NMR (CDCl3) δ 1.02 (t, 3 H, J=7.4 Hz), 1.95-2.10 (m, 1 H), 2.20-2.35 (m, 1 H), 2.75 (br s, 4 H), 3.91 (m, 4 H), 7.10-7.20 (m, 2 H), 7.40-7.48 (m, 1 H), 7.69-7.82 (m, 3 H); 13C NMR (CDCl3) δ 11.61, 25.34, 26.90, 50.26, 55.23, 105.70, 119.27, 126.31, 127.25, 127.60, 129.04, 129.57, 131.94, 134.23, 158.16, 169.28, 169.78; Anal. Calcd for C19H19NO5 : C, 66.85; H, 5.61; N, 4.10. Found: C, 65.92; H, 5.41; N, 3.64.
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1.[Cl:15][C:16]1[CH:24]=[C:23]([S:25]([CH2:28][C@@H:29]([OH:31])[CH3:30])(=[O:27])=[O:26])[CH:22]=[CH:21][C:17]=1[C:18](O)=[O:19]>>[Cl:15][C:16]1[CH:24]=[C:23]([S:25]([CH2:28][C@@H:29]([OH:31])[CH3:30])(=[O:26])=[O:27])[CH:22]=[CH:21][C:17]=1[C:18]([NH:6][C:5]1[CH:7]=[CH:8][C:2]([Cl:1])=[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[CH:4]=1)=[O:19]
Reactant: C[C@H](O)CS(=O)(=O)c1ccc(C(=O)O)c(Cl)c1
Reactant: Nc1ccc(Cl)c(-c2ccccn2)c1
Product: C[C@H](O)CS(=O)(=O)c1ccc(C(=O)Nc2ccc(Cl)c(-c3ccccn3)c2)c(Cl)c1

Procedure:
86 mg of (S)-propylene oxide was reacted with methyl 2-chloro-4-mercaptobenzoate via Procedure S to afford (S)-methyl 2-chloro-4-(2-hydroxypropylthio)benzoate. 275 mg of (S)-methyl-2-chloro-4-(2-hydroxypropylthio)benzoate was hydrolyzed via Procedure M to give (S)-2-chloro-4-(2-hydroxypropylthio)benzoic acid. 220 mg of (S)-2-chloro-4-(2-hydroxypropylthio)benzoic acid was reacted via Procedure R to give (S)-2-chloro-4-(2-hydroxypropylsulfonyl)benzoic acid. 70 mg of 4-chloro-3-(pyridine-2-yl)aniline was coupled to (S)-2-chloro-4-(2-hydroxypropylsulfonyl)benzoic acid via Procedure G. The product was purified on reverse phase HPLC to yield (S)-2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(2-hydroxypropylsulfonyl)benzamide. MS (Q1) 465.0 (M)+
Reaction SMILES: [CH3:1][N:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]([CH2:12][NH2:13])[CH2:4][CH2:3]1.F[C:15]1[CH:23]=[N:22][CH:21]=[CH:20][C:16]=1[C:17]([OH:19])=[O:18]>>[CH3:1][N:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]([CH2:12][NH:13][C:20]2[CH:21]=[N:22][CH:23]=[CH:15][C:16]=2[C:17]([OH:19])=[O:18])[CH2:4][CH2:3]1
Reactant: CN1CCC(CN)c2ccccc21
Reactant: O=C(O)c1ccncc1F
Product: CN1CCC(CNc2cnccc2C(=O)O)c2ccccc21
Yield: 18 %

Procedure:
The title compound was prepared in 18% yield from 1-(1-methyl-1,2,3,4-tetrahydroquinolin-4-yl)methanamine and 3-fluoroisonicotinic acid according to the procedure for the preparation of Example 53. 1H NMR (400 MHz, DMSO-d6): δ 13.36 (br s, 1H), 8.35 (s, 1H), 7.83 (d, 1H, J=5.0 Hz), 7.72 (br s, 1H), 7.56 (d, 1H, J=5.0 Hz), 7.01-7.08 (m, 2H), 6.52-6.62 (m, 2H), 3.45-3.51 (m, 2H), 3.04-3.32 (m, 3H), 2.85 (s, 3H), 1.89-1.95 (m, 2H). [M+H] calc'd for C17H19N3O2, 298; found 298.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl:7][C:8]1[CH:9]=[C:10]([C:20](=[O:26])[C:21](OCC)=[O:22])[CH:11]=[CH:12][C:13]=1[CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1.Cl>CCOCC>[Cl:7][C:8]1[CH:9]=[C:10]([CH:20]([OH:26])[CH2:21][OH:22])[CH:11]=[CH:12][C:13]=1[CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1
Reactant: CCOC(=O)C(=O)c1ccc(C2CCCCC2)c(Cl)c1
Agent: Cl
Agent: [Al+3]
Agent: [H-]
Solvent: CCOCC
Product: OCC(O)c1ccc(C2CCCCC2)c(Cl)c1

Procedure:
To lithium aluminum hydride solution (3.9 M; 120 ml) diluted with anhydrous ether (750 ml) is added dropwise 150 g of ethyl 3-chloro-4-cyclohexylphenylglyoxylate with stirring, under nitrogen. The mixture is diluted with 250 ml of ether, and is stirred for 2 hours. The reaction mixture is acidified with 10% hydrochloric acid (450 ml) and extracted with ether/tetrahydrofuran. The aqueous fraction is washed three times with 50 ml portions of ether. The combined ether fractions are washed with water until neutral to litmus, and is dried over potassium carbonate. The ether is removed and the residue is triturated with n-hexane, filtered and air-dried to give 1-(3-chloro-4-cyclohexylphenyl)-1,2-ethanediol.