Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([CH2:7][C@H:8]2[C@H:12]([CH2:13][C@@H:14]([CH:19]([CH3:21])[CH3:20])[CH:15]([OH:18])CO)[O:11][C:10]([CH3:23])([CH3:22])[N:9]2[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Pb+4].CCOCC>C1C=CC=CC=1>[CH:1]1([CH2:7][C@H:8]2[C@H:12]([CH2:13][C@H:14]([CH:15]=[O:18])[CH:19]([CH3:21])[CH3:20])[O:11][C:10]([CH3:22])([CH3:23])[N:9]2[C:24]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: CC(C)[C@H](C[C@@H]1OC(C)(C)N(C(=O)OC(C)(C)C)[C@H]1CC1CCCCC1)C(O)CO
Agent: CC(=O)[O-]
Agent: [Pb+4]
Solvent: c1ccccc1
Solvent: CCOCC
Product: CC(C)[C@@H](C=O)C[C@@H]1OC(C)(C)N(C(=O)OC(C)(C)C)[C@H]1CC1CCCCC1
Reaction time: 0.25 h
Yield: 85.9 %

Procedure:
20.0 g (46.8 mmol) of t-butyl (4S,5S)-4-(cyclohexylmethyl)-5-[(2S,3RS)-3,4-dihydroxy-2-isopropylbutyl]-2,2-dimethyl-3-oxazolidinecarboxylate are dissolved in 250 ml of benzene, cooled to 5° and treated portionwise within 10 minutes with 20.8 g (47 mmol) of lead tetraacetate. After stirring at 5° for 4 hours 500 ml of ether are added and the reaction mixture is stirred for a further 15 minutes. Thereafter, the reaction mixture is filtered and the filtrate is evaporated under reduced pressure. Chromatography of the residue on 300 g of silica gel with methylene chloride as the eluting agent yields 15.9 g of t-butyl (4S,5S)-4-(cyclohexylmethyl)-5-[(S)-2-formyl-3-methylbutyl]-2,2-dimethyl-3-oxazolidinecarboxylate as an oil, MS: 380 (M-CH3)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[S:9][CH2:10][CH2:11][C:12]([OH:14])=O.C(Cl)(=O)C(Cl)=O.CN(C=O)C.[Sn](Cl)(Cl)(Cl)Cl>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]2[C:4]=1[S:9][CH2:10][CH2:11][C:12]2=[O:14]
Reactant: COc1ccccc1SCCC(=O)O
Agent: Cl[Sn](Cl)(Cl)Cl
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: COc1cccc2c1SCCC2=O
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 69.8 %

Procedure:
To a solution of 3-[(2-methoxyphenyl)thio]propanoic acid (5.0 g, 23.6 mmol) in dry DCM (50 mL) at 0° C. is added oxalyl chloride (6.01 g, 4.09 mL, 47.2 mmol, 2 Eq) followed by few drops of DMF. The reaction mixture is stirred at 0° C. for 30 minutes. After 30 minutes, the solvent is removed under reduced pressure. To a solution of the acid chloride in DCM (150 mL) at 0° C. is added a solution of tin (IV) chloride in DCM (26 mL, 1 M, 26.0 mmol, 1.1 Eq) and the reaction mixture is stirred for 2 h. The reaction is quenched by addition of water and the product is extracted with DCM. The organic layer is dried over MgSO4, concentrated under reduced pressure. The crude residue is purified by flash chromatography (eluent: ethyl acetate/hexane 4/6) to afford 3.2 g of the title compound as a white solid.1H NMR (DMSO-d6, 400 MHz): δ 7.59-7.57 (m, 1H), 7.18 (m, 2H), 3.84 (s, 3H), 3.24-3.21 (m, 2H), 2.84-2.81 (m, 2H). MS (ESI+): 196.0. HPLC (max plot) 89.4%; Rt 3.36 min.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([N+:18]([O-:20])=[O:19])[CH:5]=[C:6]([CH3:17])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1.[Br:21]N1C(=O)CCC1=O.FC(F)(F)C(O)=O>C(Cl)(Cl)Cl>[Br:21][C:13]1[CH:14]=[C:9]([CH:10]=[CH:11][C:12]=1[O:15][CH3:16])[O:8][C:7]1[C:6]([CH3:17])=[CH:5][C:4]([N+:18]([O-:20])=[O:19])=[CH:3][C:2]=1[CH3:1]
Reactant: O=C1CCC(=O)N1Br
Reactant: COc1ccc(Oc2c(C)cc([N+](=O)[O-])cc2C)cc1
Solvent: ClC(Cl)Cl
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(Oc2c(C)cc([N+](=O)[O-])cc2C)cc1Br
Yield: 97.2 %

Procedure:
To a solution of 3,5-dimethyl-4-(4′-methoxyphenoxy)nitrobenzene (4.0 g) (J. Med. Chem., 38: 703 (1995)) in chloroform (150 ml) were added N-bromosuccinimide (2.6 g) and trifluoroacetic acid (1.1 ml), and the resulting mixture was heated under reflux for 90 min. Additional portions of N-bromosuccinimide (2.6 g) and trifluoroacetic acid (1.1 ml) were added, followed by further heating for 18 h. The reaction was washed with sodium bicarbonate, dried (Na2SO4) and concentrated to afford the title compound of Step A as an orange solid (5.0 g). MS (APCl+) Calc: 351; Found: 352 (M+1).
Reaction SMILES: [BH4-].[Na+].CCO.[CH2:6]([O:8][C:9](=[O:35])[CH2:10][O:11][CH2:12][CH2:13][CH2:14][CH2:15][N:16]1[C:21](=[O:22])[CH2:20][CH2:19][CH2:18][C@@H:17]1/[CH:23]=[CH:24]/[C:25](=[O:34])[CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([Cl:33])[CH:28]=1)[CH3:7]>C(Cl)Cl>[CH2:6]([O:8][C:9](=[O:35])[CH2:10][O:11][CH2:12][CH2:13][CH2:14][CH2:15][N:16]1[C:21](=[O:22])[CH2:20][CH2:19][CH2:18][C@@H:17]1/[CH:23]=[CH:24]/[CH:25]([OH:34])[CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([Cl:33])[CH:28]=1)[CH3:7]
Reactant: CCOC(=O)COCCCCN1C(=O)CCC[C@@H]1/C=C/C(=O)Cc1cccc(Cl)c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: ClCCl
Product: CCOC(=O)COCCCCN1C(=O)CCC[C@@H]1/C=C/C(O)Cc1cccc(Cl)c1
Yield: 80.4 %

Procedure:
Sodium borohydride (10 mg, 0.26 mmol) followed by EtOH (0.25 mL) was added to a solution of (4-{(R)-2-[(E)-4-(3-chlorophenyl)-3-oxo-but-1-enyl]-6-oxo -piperidin-1-yl}-butoxy)-acetic acid ethyl ester (110 mg, 0.25 mmol) in CH2Cl2 (1.0 mL) at 0° C. After 1 h at 0° C. the reaction was quenched with 1 N aqueous HCl. The reaction mixture was extracted with CH2Cl2 (3×10 mL), then the combined extracts were dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (CH2Cl2 →2% MeOH/CH2Cl2) afforded 88 mg (80%) of (4-{(R)-2-[(E)-4-(3-chlorophenyl)-3-hydroxy-but-1-enyl]-6-oxo-piperidin-1-yl}-butoxy)-acetic acid ethyl ester.
Reaction SMILES: C(O[C:5]([CH3:9])([CH3:8])[C:6]#[CH:7])(=O)C.[N:10]1([C:16]([O:18]C(C)(C)C)=O)[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.[OH-].[Na+].N>O1CCCC1.C(OCC)(=O)C>[CH3:6][C:5]([CH3:9])([CH3:8])[C:16]([N:10]1[CH2:11][CH2:12][N:13]([C:5]([CH3:8])([CH3:9])[C:6]#[CH:7])[CH2:14][CH2:15]1)=[O:18]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: C#CC(C)(C)OC(C)=O
Agent: N
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: C#CC(C)(C)N1CCN(C(=O)C(C)(C)C)CC1
Temperature: 25 °C
Yield: 157 %

Procedure:
0.756 g (6 mmol) of 1,1-dimethylprop-2-yn-1-yl acetate (J. Org. Chem. 1994, 59, 2282-4) and 2.235 g (12 mmol) of 1,1-dimethylethyl piperazine-1-carboxylate are dissolved in 9 ml of tetrahydrofuran and then 0.059 g (0.6 mmol) of cuprous chloride is added. The mixture is heated at reflux for 3 hours. After cooling to ambient temperature, 100 ml of ethyl acetate, 10 ml of 1N aqueous sodium hydroxide and 2 ml of 30% ammonia are added. The organic phase is separated off and washed with 2 times 10 ml of water and then with 10 ml of saturated aqueous sodium chloride solution. It is dried over sodium sulphate and evaporated. The product is purified by chromatography on silica gel, eluting with an 85/15 then 75/25 and 65/35 mixture of cyclohexane and ethyl acetate, to give 1.19 g (4.71 mmol) of product in the form of a pale yellow solid.
Reaction SMILES: NS(C1C=CC(C2[S:12][CH:13]=[C:14]([C:16]([OH:18])=[O:17])N=2)=CC=1)(=O)=O.[CH3:19][C:20]([CH3:34])([O:22][C:23]([C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[C:27]([NH2:33])[CH:26]=1)=[O:24])[CH3:21].S.BrCC(=O)C(OCC)=O>>[C:23]([C:25]1[CH:32]=[CH:31][C:28]([C:29]2[S:12][CH:13]=[C:14]([C:16]([OH:18])=[O:17])[N:30]=2)=[C:27]([NH2:33])[CH:26]=1)([O:22][C:20]([CH3:34])([CH3:19])[CH3:21])=[O:24]
Reactant: CC(C)(C)OC(=O)c1ccc(C#N)c(N)c1
Reactant: NS(=O)(=O)c1ccc(-c2nc(C(=O)O)cs2)cc1
Agent: CCOC(=O)C(=O)CBr
Agent: S
Product: CC(C)(C)OC(=O)c1ccc(-c2nc(C(=O)O)cs2)c(N)c1

Procedure:
In a manner similar to that described for the preparation of 2-(4-aminosulfonylphenyl)thiazole-4-carboxylic acid, 4-[(1,1-dimethylethoxy)carbonyl]-aminobenzonitrile was treated with H2S, ethyl bromopyruvate, and LIOH successively to give the title compound. MS m/z: 321 (M+H).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:16]=[CH:15][C:11]3[O:12][CH2:13][O:14][C:10]=3[CH:9]=2)[C:5]([C:17]#[N:18])=[C:4](S(C)(=O)=O)[N:3]=1.[NH2:23][CH2:24][CH2:25][N:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1>COCCOC>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:16]=[CH:15][C:11]3[O:12][CH2:13][O:14][C:10]=3[CH:9]=2)[C:5]([C:17]#[N:18])=[C:4]([NH:23][CH2:24][CH2:25][N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[N:3]=1
Reactant: CS(=O)(=O)c1nc(N)nc(-c2ccc3c(c2)OCO3)c1C#N
Reactant: NCCN1CCOCC1
Solvent: COCCOC
Product: N#Cc1c(NCCN2CCOCC2)nc(N)nc1-c1ccc2c(c1)OCO2

Procedure:
From 2-amino-4-benzo[1,3]dioxol-5-yl-6-methanesulfonyl-pyrimidine-5-carbonitrile and 4-(2-aminoethyl)morpholine in DME. ES-MS m/e (%): 369 (M+H+, 100), 282 ([M+H—C4H9NO]+, 75).
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[C:10]([O:14][CH3:15])(=[O:13])[CH:11]=[CH2:12].C1N2CCN(CC2)C1>CO>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]([OH:7])[C:11](=[CH2:12])[C:10]([O:14][CH3:15])=[O:13])=[CH:4][CH:3]=1
Reactant: C=CC(=O)OC
Reactant: O=Cc1ccc(Br)cc1
Agent: C1CN2CCN1CC2
Solvent: CO
Product: C=C(C(=O)OC)C(O)c1ccc(Br)cc1
Yield: 47.2 %

Procedure:
A solution of 2.46 g (13.3 mmol) of 4-bromobenzaldehyde, 1.0 mL (11.1 mmol) of methyl acrylate and 125 mg (1.11 mmol) of 1,4-diazobicyclo[2.2.2]octane in 5 mL MeOH was stirred at ambient temperature for 46 hr. The solvent was evaporated and the residue taken up in EtOAc. The organics were washed with 0.5 N HCl (aq), then with brine, and concentrated. The residue was purified by silica gel chromatography (120 g of silica gel eluting with 0-30% EtOAc in hexanes over 45 minutes) to give 1.42 g (40%) of methyl 2-[(4-bromophenyl)(hydroxy)methyl]-2-propenoate as a clear oil. 1H NMR (400 MHz, CDCl3): δ 7.47 (d, J=2 Hz, 2H), 7.27 (d, J=2 Hz, 2H), 6.33 (s, 1H), 5.82 (s, 1H), 5.51 (d, J=5 Hz, 1H), 3.72 (s, 3H), 3.07 (d, J=5 Hz, 1H). ESI-LCMS m/z 293 (M+Na)+.
Reaction SMILES: [C:1]1(=[C:7]2[C:12](=[O:13])[O:11][C:10]([CH3:15])([CH3:14])[O:9][C:8]2=[O:16])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:17][O:18][C:19]1[CH:20]=[C:21]([Mg]Br)[CH:22]=[CH:23][CH:24]=1.CC1C=C(COC2C=C(CCC(O)=O)C=CC=2)C=CC=1C1C=CC=C(OC)C=1>>[CH3:17][O:18][C:19]1[CH:24]=[C:23]([C:1]2([CH:7]3[C:12](=[O:13])[O:11][C:10]([CH3:14])([CH3:15])[O:9][C:8]3=[O:16])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)[CH:22]=[CH:21][CH:20]=1
Reactant: COc1cccc([Mg]Br)c1
Reactant: CC1(C)OC(=O)C(=C2CCCCC2)C(=O)O1
Agent: COc1cccc(-c2ccc(COc3cccc(CCC(=O)O)c3)cc2C)c1
Product: COc1cccc(C2(C3C(=O)OC(C)(C)OC3=O)CCCCC2)c1

Procedure:
5-(2-(3-Methoxyphenyl)propan-2-yl)-2,2-dimethyl-1,3-dioxane-4,6-dione (105.B) was prepared from 105.A and (3-methoxyphenyl)magnesium bromide (1.0 M in THF solution from Aldrich) using a procedure described in Huang, X.; et. al.; Tetrahedron Letters; 1982, (1); pp. 75-76. MS ESI (neg.) m/e: 331.1 (M−H)−.
Reaction SMILES: [H-].[Na+].[CH3:3][C:4]1([CH3:27])[O:8][C@@H:7]([CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([C:20]3[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=3)([CH3:19])[CH3:18])=[CH:13][CH:12]=2)[CH2:6][O:5]1.CC1C=CC(S(O[CH2:39][C@@H:40]2[O:42][CH2:41]2)(=O)=O)=CC=1>CN(C)C=O>[CH3:3][C:4]1([CH3:27])[O:8][C@@H:7]([CH2:9][O:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]([C:20]3[CH:21]=[CH:22][C:23]([O:26][CH2:39][C@H:40]4[CH2:41][O:42]4)=[CH:24][CH:25]=3)([CH3:18])[CH3:19])=[CH:15][CH:16]=2)[CH2:6][O:5]1
Reactant: Cc1ccc(S(=O)(=O)OC[C@H]2CO2)cc1
Reactant: CC1(C)OC[C@H](COc2ccc(C(C)(C)c3ccc(O)cc3)cc2)O1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC1(C)OC[C@H](COc2ccc(C(C)(C)c3ccc(OC[C@H]4CO4)cc3)cc2)O1
Reaction time: 0.5 h
Yield: 97.4 %

Procedure:
Sodium hydride (60% dispersion in mineral oil, 391 mg, 9.78 mmol, 1.5 equiv) was added slowly to a stirred solution of (S)-4-(2-(4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)propan-2-yl)phenol (2230 mg, 6.52 mmol, 1 equiv) in anhydrous dimethyl formamide (15 mL), at room temperature, and the contents were stirred under an atmosphere of argon for 30 min. A solution of (2R)-(−)-glycidyl tosylate 98% (2230 mg, 9.78 mmol, 1.5 equiv) in anhydrous dimethyl formamide (5 mL) was added via syringe and the mixture was allowed to react at room temperature for 16 h. Then, the reaction was quenched by the addition of a saturated solution of ammonium chloride (10 mL), and the mixture was extracted with ethyl acetate (3×20 mL). The organic layer was washed with deionized water (20 mL), dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel (eluent: 20% to 40% ethyl acetate in hexane) to provide the title compound (2.53 g, 94%) as a clear foam.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[O:9][CH:10]=[CH:11][CH:12]=2)[C:5]([C:13]#[N:14])=[C:4](S(C)=O)[N:3]=1.[CH3:18][C:19]1[CH:24]=[CH:23][N:22]=[C:21]([CH2:25][OH:26])[CH:20]=1.C1CCN2C(=NCCC2)CC1>COCCOC>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[O:9][CH:10]=[CH:11][CH:12]=2)[C:5]([C:13]#[N:14])=[C:4]([O:26][CH2:25][C:21]2[CH:20]=[C:19]([CH3:18])[CH:24]=[CH:23][N:22]=2)[N:3]=1
Reactant: Cc1ccnc(CO)c1
Reactant: CS(=O)c1nc(N)nc(-c2ccco2)c1C#N
Solvent: COCCOC
Solvent: C1CCC2=NCCCN2CC1
Product: Cc1ccnc(COc2nc(N)nc(-c3ccco3)c2C#N)c1

Procedure:
From 2-amino-4-furan-2-yl-6-methanesulfinyl-pyrimidine-5-carbonitrile, (4-methyl-pyridin-2-yl)methanol and DBU in DME. ES-MS m/e (%): 308 (M+H+, 100).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:28]=[C:29]([O:33][CH3:34])[C:30]=1[O:31][CH3:32])[C:6]([N:8]1[CH2:12][CH2:11][C@:10]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)([CH2:13][CH2:14]OS(C)(=O)=O)[CH2:9]1)=[O:7].[CH2:35]([O:37][CH2:38][CH2:39][N:40]1[C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=2[N:42]=[C:41]1[N:49]1[CH2:55][CH2:54][CH2:53][NH:52][CH2:51][CH2:50]1)[CH3:36]>>[CH3:34][O:33][C:29]1[CH:28]=[C:5]([CH:4]=[C:3]([O:2][CH3:1])[C:30]=1[O:31][CH3:32])[C:6]([N:8]1[CH2:12][CH2:11][C@@:10]([CH2:13][CH2:14][N:52]2[CH2:53][CH2:54][CH2:55][N:49]([C:41]3[N:40]([CH2:39][CH2:38][O:37][CH2:35][CH3:36])[C:44]4[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=4[N:42]=3)[CH2:50][CH2:51]2)([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([Cl:27])[CH:21]=2)[CH2:9]1)=[O:7]
Reactant: COc1cc(C(=O)N2CC[C@@](CCOS(C)(=O)=O)(c3ccc(Cl)c(Cl)c3)C2)cc(OC)c1OC
Reactant: CCOCCn1c(N2CCCNCC2)nc2ccccc21
Product: CCOCCn1c(N2CCCN(CC[C@@]3(c4ccc(Cl)c(Cl)c4)CCN(C(=O)c4cc(OC)c(OC)c(OC)c4)C3)CC2)nc2ccccc21

Procedure:
Prepare by the method of Example 1.6 using (R)-1-(3,4,5-trimethoxybenzoyl)-3-(3,4-dichlorophenyl)-3-(2-methanesulfonyloxyethyl)pyrrolidine and 4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane to give the title compound.
Reaction SMILES: Cl.[Br:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1.C(N(CC)CC)C.Cl[C:23]1[N:28]([CH3:29])[C:27](=[O:30])[CH:26]=[C:25]([C:31]2[CH:36]=[CH:35][N:34]=[CH:33][CH:32]=2)[N:24]=1>O1CCCC1>[Br:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:10][CH2:11][N:12]([C:23]3[N:28]([CH3:29])[C:27](=[O:30])[CH:26]=[C:25]([C:31]4[CH:32]=[CH:33][N:34]=[CH:35][CH:36]=4)[N:24]=3)[CH2:13][CH2:14]2)=[CH:5][CH:4]=1
Reactant: Brc1ccc(C2CCNCC2)cc1
Reactant: Cn1c(Cl)nc(-c2ccncc2)cc1=O
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Cn1c(N2CCC(c3ccc(Br)cc3)CC2)nc(-c2ccncc2)cc1=O
Yield: 93.1 %

Procedure:
A solution of (4-(4-bromophenyl)-piperidine hydrochloride (279 mg, 1.01 mmol) and triethylamine (554 mg, 5.47 mmol), 2-chloro-3-methyl-6-(pyridin-4-yl)-3H-pyrimidin-4-one (206 mg, 0.929 mmol) in tetrahydrofuran (20 mL) was stirred for 3 hr. The resulting solution was diluted with tetrahydrofuran and filtrated. After removal of the solvents under reduced pressure and the purification of the resulting residue by CHEM ELUT CE1010 (manufactured by VARIAN) eluting dichloromethane/ethanol (15/1, v/v) and wash with ethyl acetate afforded 2-(4-(4-Bromophenyl)-piperidin-1-yl)-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one (368 mg, 93%) as a solid.
Reaction SMILES: [OH:1][C:2]1[C:7]2[O:8][C:9]([C:11]3[O:12][C:13]([CH3:16])=[CH:14][N:15]=3)=[CH:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.S(C1C=CC([N+]([O-])=O)=CC=1)(O[CH2:21][C@H:22]1[O:24][CH2:23]1)(=O)=O>>[CH2:21]([O:1][C:2]1[C:7]2[O:8][C:9]([C:11]3[O:12][C:13]([CH3:16])=[CH:14][N:15]=3)=[CH:10][C:6]=2[CH:5]=[CH:4][CH:3]=1)[C@H:22]1[O:24][CH2:23]1
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)OC[C@@H]2CO2)cc1
Reactant: Cc1cnc(-c2cc3cccc(O)c3o2)o1
Product: Cc1cnc(-c2cc3cccc(OC[C@@H]4CO4)c3o2)o1
Yield: 79.6 %

Procedure:
By the reactions in the same manner as in Starting Material Synthesis Example 1 using 2-(7-hydroxybenzo(b)furan-2-yl)-5-methyloxazole (2.0 g) obtained in Starting Material Synthesis Example 65 and (S)-glycidyl nosylate (1.8 g), (S)-7-glycidyloxy-2-(5-methyloxazol-2-yl)benzo(b)furan (1.5 g) was obtained. Then, by the reactions in the same manner as in Example 1 using 4-(naphthalen-2-yl)piperidine (0.7 g), the title compound (0.26 g) was obtained, melting point 147–149° C.
Reaction SMILES: C(N(C(C)C)CC)(C)C.Br.[Br:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[N:19]=[C:20]([NH:24][C:25]([CH3:29])([CH3:28])[CH2:26][OH:27])[S:21][C:22]=2[CH3:23])=[CH:14][CH:13]=1.Cl[C:31](Cl)([O:33]C(=O)OC(Cl)(Cl)Cl)Cl>C(Cl)Cl>[Br:11][C:12]1[CH:13]=[CH:14][C:15]([C:18]2[N:19]=[C:20]([N:24]3[C:25]([CH3:29])([CH3:28])[CH2:26][O:27][C:31]3=[O:33])[S:21][C:22]=2[CH3:23])=[CH:16][CH:17]=1
Reactant: Cc1sc(NC(C)(C)CO)nc1-c1ccc(Br)cc1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Agent: Br
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cc1sc(N2C(=O)OCC2(C)C)nc1-c1ccc(Br)cc1
Reaction time: 2 h
Yield: 1270.7 %

Procedure:
Diisopropylethylamine (10.0 mL, 57.4 mmol) was added under nitrogen to a mixture of 2-{[4-(4-bromophenyl)-5-methyl-1,3-thiazol-2-yl]amino}-2-methylpropan-1-ol hydrobromide (5.2 g, 1.2 mmol), prepared in the previous step, and 120 mL of methylene chloride at room temperature. A white solid formed. The mixture was cooled to ice bath temperature and triphosgene (5.2 g, 1.8 mmol) in 60 mL of methylene chloride was added dropwise over approximately 2 h. After the addition, the reaction became homogeneous. The reaction was stirred at ice bath temperature for approximately 2 h and then at room temperature overnight. The reaction was extracted with aqueous sodium hydroxide and the solvent removed under reduced pressure to give 5.6 g of a solid. Purification of the solid on a Horizon™ Flash Collector (the Biotage FLASH 25+™ cartridge) using a linear gradient of 36% methylene chloride in hexane to 75% methylene chloride in hexane gave the title compound (2.77 g, 63%) as a white solid, mp 175-176.5° C.; MS (ESI) m/z 367 [M+H]+. Anal. Calcd for C15H15BrN2O2S: C, 49.06; H, 4.12; N, 7.63. Found: C, 48.94; H, 4.19; N, 7.56.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12](=[O:16])[CH2:13][CH2:14][Cl:15])[NH:8][C:7](=[O:17])[CH2:6][CH2:5]2.[CH3:18][S:19](Cl)(=[O:21])=[O:20].CN1CCC(=C2C3C(=CC=CC=3)C=CC3C2=CC=CC=3)CC1.[Cl-].[Na+]>CN(C)C=O.N1C=CC=CC=1>[CH3:18][S:19]([O:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[C:12](=[O:16])[CH2:13][CH2:14][Cl:15])[NH:8][C:7](=[O:17])[CH2:6][CH2:5]2)(=[O:21])=[O:20]
Reactant: CS(=O)(=O)Cl
Reactant: O=C1CCc2cc(O)c(C(=O)CCCl)cc2N1
Agent: CN1CCC(=C2c3ccccc3C=Cc3ccccc32)CC1
Agent: [Cl-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: c1ccncc1
Product: CS(=O)(=O)Oc1cc2c(cc1C(=O)CCCl)NC(=O)CC2
Temperature: 25 °C
Reaction time: 3 h

Procedure:
5.06 Grams of 6-hydroxy-7-(3-chloropropionyl)-3,4-dihydrocarbostyril and 1.8 g of anhydrous pyridine were mixed with 50 ml of dimethylformamide. Then the mixture was cooled with ice and 2.5 g of methanesulfonyl chloride was added to the mixture and stirred at a room temperature for 3 hours. The reactin mixture was poured into 100 ml of a saturated sodium chloride solution and extracted with chloroform. The chloroform layer was washed with water, dried and chloroform was removed by distillation under a reduced pressure to obtain a residue. The residue was crystallized by adding 80 ml of hexane to obtain crude crystals. The crude materials were collected by filtration and were recrystallized from ethanol to obtain 4.5 g of 6-methylsulfonyloxy-7-(3-chloropropionyl)-3,4-dihydrocarbostyril in white crystals.
Reaction SMILES: Cl[CH2:2][C@@H:3]1[O:7][C:6](=[O:8])[N:5]([C:9]2[CH:14]=[CH:13][C:12]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[C:11]([F:21])[CH:10]=2)[CH2:4]1.[C:22]1(=[O:32])[NH:26][C:25](=[O:27])[C:24]2=[CH:28][CH:29]=[CH:30][CH:31]=[C:23]12.[K].CN(C)C=O>O>[F:21][C:11]1[CH:10]=[C:9]([N:5]2[CH2:4][C@H:3]([CH2:2][N:26]3[C:25](=[O:27])[C:24]4=[CH:28][CH:29]=[CH:30][CH:31]=[C:23]4[C:22]3=[O:32])[O:7][C:6]2=[O:8])[CH:14]=[CH:13][C:12]=1[N:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1
Reactant: O=C1NC(=O)c2ccccc21
Reactant: O=C1O[C@@H](CCl)CN1c1ccc(N2CCOCC2)c(F)c1
Agent: [K]
Solvent: O
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1C[C@H]1CN(c2ccc(N3CCOCC3)c(F)c2)C(=O)O1
Temperature: 25 °C
Yield: 61.7 %

Procedure:
The mixture of (5R)-5-(chloromethyl)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxazolidinone (60 g), potassium phthalimide (40 g) and Dimethyl formamide (400 ml) is heated for 5 hours at reflux temperature. The reaction mixture is cooled to ambient temperature, poured in to 2 L water and filtered the solid to give 50 gm (S)-N-[[3-[3-Fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]phthalimide.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([C@@H:9]2[CH2:11][C@H:10]2[C:12]2[N:16]([CH3:17])[C:15]3[CH:18]=[CH:19][CH:20]=[CH:21][C:14]=3[N:13]=2)[CH:3]=1.O.[NH2:23][NH2:24].C(=O)([O-])[O-].[K+].[K+]>CC1OCCC1>[NH:23]([C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([C@@H:9]2[CH2:11][C@H:10]2[C:12]2[N:16]([CH3:17])[C:15]3[CH:18]=[CH:19][CH:20]=[CH:21][C:14]=3[N:13]=2)[CH:3]=1)[NH2:24]
Reactant: NN
Reactant: Cc1nc(Cl)cc([C@@H]2C[C@H]2c2nc3ccccc3n2C)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC1CCCO1
Solvent: O
Product: Cc1nc(NN)cc([C@@H]2C[C@H]2c2nc3ccccc3n2C)n1
Temperature: 25 °C

Procedure:
A slurry of 6-4 (4 g, 13.39 mmol), hydrazine hydrate (1.261 ml, 40.2 mmol) and potassium carbonate (5.55 g, 40.2 mmol) in 2-MeTHF (100 ml) was heated at 80° C. for 16 h. After cooling to room temperature, the reaction mixture was partitioned between water and ethyl acetate. The organic layer was separated, dried over sodium sulfate, filtered and concentrated to afford Intermediate 6 as a tan solid. MS: m/z=295.4 (M+H).
Reaction SMILES: [CH3:1][CH:2]([OH:9])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:29][NH:30][S:31]([C:34]1[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][CH:35]=1)(=[O:33])=[O:32].COCCOC(N=NC(OCCOC)=O)=O>C1COCC1>[CH3:40][C:37]1[CH:38]=[CH:39][C:34]([S:31]([N:30]([CH3:29])[CH:2]([CH3:1])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])(=[O:33])=[O:32])=[CH:35][CH:36]=1.[CH3:1][CH:2]([OH:9])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CNS(=O)(=O)c1ccc(C)cc1
Agent: COCCOC(=O)N=NC(=O)OCCOC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: CCCCCCC(C)O
Product: CCCCCCC(C)N(C)S(=O)(=O)c1ccc(C)cc1
Reaction time: 21 h

Procedure:
After (racemic)-2-octanol (300 mg, 2.30 mmol), triphenylphosphine (727 mg, 2.76 mmol), N-methyl-p-toluenesulfonamide (514 mg, 2.76 mmol), and THF (12 ml) were added to a 50 ml flask, azodicarboxylic acid bis(2-methoxyethyl) ester (648 mg, 2.76 mmol) dissolved in THF (6 ml) was added dropwise thereto at 20° C., and the reaction was allowed to proceed for 21 hours. Subsequently, a crude product obtained by concentration was purified by column chromatography (silica gel, 10% ethyl acetate-hexane solution) to give 4,N-dimethyl-N-(1-methylheptyl)benzenesulfonamide as a white solid substance (223 mg, yield: 33%/(racemic)-2-octanol).
Reaction SMILES: [F:1][CH:2]([F:15])[CH2:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([CH3:14])=[C:9]([C:11](=O)[CH3:12])[CH:10]=1.[CH3:16][C:17]([S@:20]([NH2:22])=[O:21])([CH3:19])[CH3:18]>>[F:1][CH:2]([F:15])[CH2:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([CH3:14])=[C:9]([CH:11]([NH:22][S@@:20]([C:17]([CH3:19])([CH3:18])[CH3:16])=[O:21])[CH3:12])[CH:10]=1
Reactant: CC(=O)c1cc(OCC(F)F)ccc1C
Reactant: CC(C)(C)[S@](N)=O
Product: Cc1ccc(OCC(F)F)cc1C(C)N[S@](=O)C(C)(C)C
Yield: 61 %

Procedure:
The title compound is prepared in 61% yield (400 mg, clear colorless oil) from 1-(5-(2,2-difluoroethoxy)-2-methylphenyl)ethanone (440 mg, 2.1 mmol, Step-4) and (R)-2-methylpropane-2-sulfinamide by the similar manner in Step-4 of Amine-1.