Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CC1N=C(C2C=CC=CC=2C([NH:11][C@H:12]2[CH2:16][CH2:15][CH2:14][C@@H:13]2[NH:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][N:19]=2)=O)ON=1.[F:32][C:33]1[CH:34]=[CH:35][C:36]([N:42]2[N:46]=[CH:45][CH:44]=[N:43]2)=[C:37]([CH:41]=1)[C:38]([OH:40])=O.Cl.FC(F)(F)C1C=CC(N[C@H]2CCC[C@@H]2N)=NC=1>>[F:32][C:33]1[CH:34]=[CH:35][C:36]([N:42]2[N:46]=[CH:45][CH:44]=[N:43]2)=[C:37]([CH:41]=1)[C:38]([NH:11][C@H:12]1[CH2:16][CH2:15][CH2:14][C@@H:13]1[NH:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:25])[F:26])=[CH:20][N:19]=1)=[O:40]
Reactant: Cc1noc(-c2ccccc2C(=O)N[C@H]2CCC[C@@H]2Nc2ccc(C(F)(F)F)cn2)n1
Reactant: O=C(O)c1cc(F)ccc1-n1nccn1
Agent: Cl
Agent: N[C@H]1CCC[C@@H]1Nc1ccc(C(F)(F)F)cn1
Product: O=C(N[C@H]1CCC[C@@H]1Nc1ccc(C(F)(F)F)cn1)c1cc(F)ccc1-n1nccn1

Procedure:
Prepared according to the procedure for 2-(3-methyl-1,2,4-oxadiazol-5-yl)-N-[(1S,2S)-2-{[5-(trifluoromethyl)pyridin-2-yl]amino}cyclopentyl]benzamide (Example 8) from 5-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoic acid (Intermediate 8; 72 mg, 0.26 mmol) and (1S,2S)-1-N-[5-(trifluoromethyl)pyridin-2-yl]cyclopentane-1,2-diamine hydrochloride (Intermediate 1; 61 mg, 0.28 mmol) to afford the title compound.
Reaction SMILES: [NH2:1][NH2:2].[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11](=O)[CH2:12][C:13](=O)[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:7][CH:6]=1>C(O)C>[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[NH:1][N:2]=2)=[CH:7][CH:6]=1
Reactant: CCOC(=O)C(=O)CC(=O)c1ccc(OC)cc1
Reactant: NN
Solvent: CCO
Product: CCOC(=O)c1cc(-c2ccc(OC)cc2)n[nH]1
Temperature: 60 °C
Reaction time: 4 h
Yield: 96.5 %

Procedure:
1.52 ml (31.28 mmol) of hydrazine was added to an ethanol solution (50 ml) of 7.12 g (28.44 mmol) of the obtained ethyl 4-(4-methoxyphenyl)-2,4-dioxobutyrate, and then the reaction liquid was stirred at 60° C. for 4 hours. The reaction liquid was concentrated under reduced pressure, and the resulting solid was washed with diethyl ether to obtain 6.76 g (yield: 96%) of ethyl 5-(4-methoxyphenyl)-2H-pyrazole-3-carboxylate as a white solid.
Reaction SMILES: [OH-].[Na+].C([O:5][C:6](=[O:21])[C:7](=[O:20])[C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[CH2:13][CH:12]([CH:17]([CH3:19])[CH3:18])[CH2:11]2)C>O.C(O)C>[CH:17]([CH:12]1[CH2:11][C:10]2[C:14](=[CH:15][CH:16]=[C:8]([C:7](=[O:20])[C:6]([OH:21])=[O:5])[CH:9]=2)[CH2:13]1)([CH3:19])[CH3:18]
Reactant: CCOC(=O)C(=O)c1ccc2c(c1)CC(C(C)C)C2
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CC(C)C1Cc2ccc(C(=O)C(=O)O)cc2C1

Procedure:
A solution of 10 g of sodium hydroxide in 20 cc of water is added to a solution of 24.5 g of crude 2-isopropyl-α-oxo-5-indanacetic acid ethyl ester in 300 cc of ethanol, and the mixture is boiled at reflux for 11/2 hours. The solution is concentrated, diluted with water, and the neutral by-products are extracted with ether. The aqueous phase is then acidified with hydrochloric acid, extracted with ether, the ether extract is washed with water, dried over sodium sulphate and concentrated by evaporation. 2-isopropyl-α-oxo-5-indanacetic acid is obtained as an oil and is used for the next reaction without purification. The (1,3-dihydroxy-2-hydroxymethyl-2-propyl)ammonium salt of 2-isopropyl-α-oxo-5-indanacetic acid has a M.P. of B 145°-147°.
Reaction SMILES: [NH2:1][C@H:2]([C:9]([OH:11])=[O:10])[CH2:3][CH2:4][P:5](Cl)([CH3:7])=[O:6].C1[O:15]C1C>C(O)C.O>[NH2:1][C@H:2]([C:9]([OH:11])=[O:10])[CH2:3][CH2:4][P:5]([CH3:7])(=[O:15])[OH:6]
Reactant: CP(=O)(Cl)CC[C@H](N)C(=O)O
Reactant: CC1CO1
Solvent: CCO
Solvent: O
Product: CP(=O)(O)CC[C@H](N)C(=O)O
Reaction time: 24 h
Yield: 81 %

Procedure:
0.33 g (0.0015 mol) of L-homoalanin-4-yl(methyl)phosphinic acid chloride are dissolved in 15 ml of ethanol/water and mixed with 0.3 g (0.005 mol) of propeneoxide. After allowing to stand for one day at room temperature, 0.22 g (80.1% of theory) of L-homoalanin-4-yl(methyl)phosphinic acid is obtained as a white solid with a melting point of 212°-214° C. (decomposes); [α]D22 =14.7° (c=0.984 in H2O).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([OH:14])[CH2:13][CH2:12][NH:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.C(#N)C.C(=O)([O-])[O-].[K+].[K+].I[CH2:25][CH2:26][CH3:27]>O>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([OH:14])[CH2:13][CH2:12][N:11]([CH2:25][CH2:26][CH3:27])[CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1
Reactant: OC1(c2cc(F)cc(Cl)c2)CCNC1
Reactant: CCCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC#N
Product: CCCN1CCC(O)(c2cc(F)cc(Cl)c2)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 44.2 %

Procedure:
A mixture of 3-(3-chloro-5-fluorophenyl)pyrrolidin-3-ol (1.10 g, 5 mmol), acetonitrile (20 mL), potassium carbonate (1.4 g, 10.1 mmol) and iodopropane (1.13 mg, 6.65 mmol) was stirred at ambient temperature for 2 h. The temperature was shortly raised to 40° C. twice during this period. Water was added and the aqueous phase was extracted with ethyl acetate, the combined organic phase was dried (MgSO4), and evaporated. Purification by flash chromatography on silica gel (ethyl acetate/methanol, 1:0 to 1:1) gave the title compound (0.57 g). The amine was converted to the oxalic acid salt and recrystallized from ethanol/diisopropyl ether: M.p. 157.2° C.; MS m/z (relative intensity, 70 eV) 257 (M+, 8), 228 (bp), 198 (46), 129 (36), 84 (59).
Reaction SMILES: [NH2:1][C:2]1[C:3]([NH:9][CH2:10][CH2:11]O)=[N:4][CH:5]=[N:6][C:7]=1[Cl:8].[C:13]([O:16][C:17](=[O:19])[CH3:18])(=O)[CH3:14]>>[C:17]([O:16][CH2:13][CH2:14][N:9]1[C:3]2[N:4]=[CH:5][N:6]=[C:7]([Cl:8])[C:2]=2[N:1]=[C:10]1[CH3:11])(=[O:19])[CH3:18]
Reactant: Nc1c(Cl)ncnc1NCCO
Reactant: CC(=O)OC(C)=O
Product: CC(=O)OCCn1c(C)nc2c(Cl)ncnc21
Yield: 21 %

Procedure:
2-(5-Amino-6-chloro-4-pyrimidinylamino)ethanol (Chem. Pharm. Bull., 1961, 9, 27) (5.71 g, 30.3 mmol) and acetic anhydride (50 ml) were heated together under nitrogen at 120° C. for 20 hours. The excess reagent was removed under reduced pressure and the residue was neutralised with aqueous sodium bicarbionate and extracted with dichloromethane (4×70 ml). The extracts were dried (MgSO4) and concentrated under reduced pressure. The residue was purified by flash chromatography (eluting with ethyl acetate) to give 3-(2-acetoxyethyl)-2-methyl-7-chlorimidazo-[4,5-d]pyrimidine (1.597 g, 21%), as a white solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:30](Cl)(=[O:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C(Cl)Cl>[C:30]([N:13]1[CH2:14][CH2:15][CH:10]([CH:9]([C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)[NH:8][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH2:11][CH2:12]1)(=[O:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: Fc1ccc(NC(c2ccc(F)cc2)C2CCNCC2)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(c1ccccc1)N1CCC(C(Nc2ccc(F)cc2)c2ccc(F)cc2)CC1

Procedure:
A solution of N,α-bis(4-fluorophenyl)-4-piperidinemethanamine (3.21 g, 0.0106 mol), triethylamine (2.5 g, 0.025 mol), and benzoyl chloride (1.70 g, 0.012 mol) in 400 mL of methylene chloride was stirred 16 h at room temperature. The reaction was concentrated to dryness and dissolved in chloroform. The chloroform layer was extracted successively with water, 1N sulfuric acid, and 5% sodium hydroxide. The chloroform layer was dried (Na2SO4) and filtered. The chloroform was removed to give a fluffy-white residue. This material was dissolved in methylene chloride and chromatographed by flash chromatography on silica gel. Elution was accomplished using methylene chloride, 1% acetone-methylene chloride, 2% acetone-methylene chloride, and 4% acetone-methylene chloride. Fractions of similar purity were combined, and solvents removed to give a fluffy-white residue. This material was triturated with isopropyl ether and chilled in a freezer. A white solid was isolated and dried, 16 h at 78° C. This furnished 1.40 g (32.5%) of white crystalline solid, mp 157°-158° C.
Reaction SMILES: C(=O)([O-])O.[Na+].C([O:9][C:10]1[CH:15]=[CH:14][C:13]([C:16](=[O:40])[N:17]([CH2:19][C:20]2[CH:21]=[C:22]([C:26]3[CH:31]=[CH:30][C:29]([CH2:32][CH:33]4[S:37][C:36](=[O:38])[NH:35][C:34]4=[O:39])=[CH:28][CH:27]=3)[CH:23]=[CH:24][CH:25]=2)[CH3:18])=[CH:12][CH:11]=1)(=O)C.Cl>O1CCCC1.O.C(OC(=O)C)C>[O:38]=[C:36]1[NH:35][C:34](=[O:39])[CH:33]([CH2:32][C:29]2[CH:28]=[CH:27][C:26]([C:22]3[CH:23]=[CH:24][CH:25]=[C:20]([CH2:19][N:17]([CH3:18])[C:16](=[O:40])[C:13]4[CH:12]=[CH:11][C:10]([OH:9])=[CH:15][CH:14]=4)[CH:21]=3)=[CH:31][CH:30]=2)[S:37]1
Reactant: CC(=O)Oc1ccc(C(=O)N(C)Cc2cccc(-c3ccc(CC4SC(=O)NC4=O)cc3)c2)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Solvent: CCOC(C)=O
Product: CN(Cc1cccc(-c2ccc(CC3SC(=O)NC3=O)cc2)c1)C(=O)c1ccc(O)cc1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
110 mg (1.3 mmol) of sodium hydrogen carbonate are added to 350 mg (6.7 mmol) of 4-{[4′-(2,4-dioxothiazolidin-5-ylmethyl)biphenyl-3-ylmethyl]methylcarbamoyl}phenyl acetate (obtained in Example 56) in 5 ml of tetrahydrofuran and 500 μl of water. The reaction medium is stirred at room temperature for 48 hours and then diluted in ethylacetate and acidified to pH 3-4 with 1N hydrochloric acid solution. The organic phase is separated out after settling of the phases has taken place, dried over sodium sulfate, filtered and evaporated. The residue obtained is purified by chromatography on a column of silica eluted with a 99/1 dichloromethane/methanol mixture. After evaporation of the solvents, 250 mg (83%) of N-[4′(2,4-dioxothiazolidin-5-ylmethyl)-biphenyl-3-ylmethyl]-4-hydroxy-N-methylbenzamide are collected in the form of a white powder with a melting point of 110° C.
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[O:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].CS(O[CH2:26][C:27]1([CH2:30][O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:29][CH2:28]1)(=O)=O.O>CN(C=O)C>[CH2:32]([O:31][CH2:30][C:27]1([CH2:26][N:12]2[CH:13]=[C:9]([B:4]3[O:5][C:6]([CH3:7])([CH3:8])[C:2]([CH3:14])([CH3:1])[O:3]3)[CH:10]=[N:11]2)[CH2:29][CH2:28]1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Reactant: CS(=O)(=O)OCC1(COCc2ccccc2)CC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: CC1(C)OB(c2cnn(CC3(COCc4ccccc4)CC3)c2)OC1(C)C
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 73.4 %

Procedure:
A solution of (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (8.62 g, 44.4 mmol) in DMF (12 mL) was treated with cesium carbonate (14.6 g, 44.4 mmol) and stirred at RT for 10 min. A solution of {1-[(benzyloxy)methyl]cyclopropyl}methyl methanesulfonate (Compound 63D, 12 g, 44.4 mmol) in DMF was added and heated to 70° C. for 24 hrs. The reaction mixture was cooled to RT, poured into water, extracted with ethyl acetate, dried over sodium sulfate, filtered and concentrated to give 12 g (73%) of required compound as a colorless gum which was used without further purification. 1H NMR (600 MHz, CDCl3) δ 7.78 (s, 1H), 7.68 (s, 1H), 7.25-7.34 (m, 5H), 4.48 (s, 2H), 4.15 (s, 2H), 3.16 (s, 2H), 1.33 (s, 12H), 0.71 (s, 2H), 0.56 (s, 2H).
Reaction SMILES: [Cl:1][C:2]1[S:6][C:5]([C:7](=O)[CH2:8][C:9]2[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[CH:16]([NH:20][NH2:21])([CH2:18][CH3:19])[CH3:17].[CH2:22](N(CC)CC)C>ClCCl>[CH:16]([N:20]1[CH:22]=[C:8]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=2)[C:7]([C:5]2[S:6][C:2]([Cl:1])=[CH:3][CH:4]=2)=[N:21]1)([CH2:18][CH3:19])[CH3:17].[CH:16]([N:20]1[C:7]([C:5]2[S:6][C:2]([Cl:1])=[CH:3][CH:4]=2)=[C:8]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=2)[CH:22]=[N:21]1)([CH2:18][CH3:19])[CH3:17]
Reactant: O=C(Cc1ccncc1)c1ccc(Cl)s1
Reactant: CCC(C)NN
Reactant: CCN(CC)CC
Solvent: ClCCl
Product: CCC(C)n1cc(-c2ccncc2)c(-c2ccc(Cl)s2)n1
Product: CCC(C)n1ncc(-c2ccncc2)c1-c1ccc(Cl)s1
Yield: 16 %
Yield: 21 %

Procedure:
A mixture of 1-(5-chloro-2-thienyl)-2-(pyridin-4-yl)ethanone (0.68 mmol), secbutylhydrazin (1.37 mmol) and triethylamine (1.37 mmol) in 5 mL dichloromethane was refluxed for 2.5 h. The solvent was evaporated under reduced pressure and the residue was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate and the combined organic extracts were dried over MgSO4 filtered and concentrated. The residue was purified by chromatography on silica gel (dichloromethane:methanol 100:1 to 20:1) to afford 37 mg of 4-[1-sec-butyl-3-(5-chloro-2-thienyl)-1H-pyrazol-4-yl]pyridine (16% yield) and 48 mg of 4-[1-sec-butyl-5-(5-chloro-2-thienyl)-1H-pyrazol-4-yl]pyridine (21% yield).
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([F:15])([F:14])[F:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.[NH2:16][C:17]1[CH:39]=[CH:38][C:20]([C:21]([N:23]2[CH2:28][CH2:27][CH:26]([CH:29]([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)[OH:30])[CH2:25][CH2:24]2)=[O:22])=[CH:19][CH:18]=1>C(O)C>[ClH:1].[F:37][C:34]1[CH:33]=[CH:32][C:31]([CH:29]([OH:30])[CH:26]2[CH2:27][CH2:28][N:23]([C:21](=[O:22])[C:20]3[CH:19]=[CH:18][C:17]([NH:16][C:2]4[C:11]5[C:6](=[CH:7][C:8]([C:12]([F:15])([F:14])[F:13])=[CH:9][CH:10]=5)[N:5]=[CH:4][CH:3]=4)=[CH:39][CH:38]=3)[CH2:24][CH2:25]2)=[CH:36][CH:35]=1
Reactant: FC(F)(F)c1ccc2c(Cl)ccnc2c1
Reactant: Nc1ccc(C(=O)N2CCC(C(O)c3ccc(F)cc3)CC2)cc1
Solvent: CCO
Product: Cl
Product: O=C(c1ccc(Nc2ccnc3cc(C(F)(F)F)ccc23)cc1)N1CCC(C(O)c2ccc(F)cc2)CC1
Yield: 84.7 %

Procedure:
A mixture of 4-chloro-7-(trifluoromethyl)quinoline (0.32 g) and 1-(4-aminobenzoyl)-4-[(4-fluorophenyl)hydroxymethyl]piperidine (0.45 g) in dry ethanol (10 ml) was stirred under reflux for 4 hours and concentrated to dryness in vacuo. The residue was recrystallized from a mixture of ethyl acetate and isopropanol to give 4-[(4-fluorophenyl)hydroxymethyl]-1-[4-[[7-(trifluoromethyl)-4-quinolyl]amino]benzoyl]piperidine hydrochloride (0.65 g) as pale yellow powder.
Reaction SMILES: N(CC)CC.S([O-])([O-])(=O)=O.C1C2C(COC([N:28]3[CH2:33][CH2:32][CH:31]([C:34]4[O:38][N:37]=[C:36]([C@@H:39]5[CH2:45][CH2:44][C@@H:43]6[CH2:46][N:40]5[C:41](=[O:52])[N:42]6[O:47][S:48]([OH:51])(=[O:50])=[O:49])[N:35]=4)[CH2:30][CH2:29]3)=O)C3C(=CC=CC=3)C=2C=CC=1.C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC>C(Cl)Cl>[S:48]([OH:51])([O:47][N:42]1[C:41](=[O:52])[N:40]2[CH2:46][C@H:43]1[CH2:44][CH2:45][C@H:39]2[C:36]1[N:35]=[C:34]([CH:31]2[CH2:32][CH2:33][NH:28][CH2:29][CH2:30]2)[O:38][N:37]=1)(=[O:49])=[O:50]
Reactant: O=C(OCC1c2ccccc2-c2ccccc21)N1CCC(c2nc([C@@H]3CC[C@@H]4CN3C(=O)N4OS(=O)(=O)O)no2)CC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=S(=O)([O-])[O-]
Solvent: CCNCC
Solvent: ClCCl
Product: O=C1N2C[C@@H](CC[C@H]2c2noc(C3CCNCC3)n2)N1OS(=O)(=O)O
Temperature: 25 °C
Reaction time: 12 h
Yield: 24.1 %

Procedure:
Et2NH (0.5 mL, 5.0 mmol)) was added to a solution of tetrabutylammonium (9H-fluoren-9-yl)methyl 4-(3-((2S,5R)-7-oxo-6-(sulfooxy)-1,6-diaza-bicyclo[3.2.1]octan-2-yl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate sulfate (84 mg, 0.1 mmol) in dry DCM (10 mL. The mixture was stirred at rt for 12 hrs and the solvents were evaporated under vacuum. The residue was purified by prep-HPLC to afford (2S,5R)-7-oxo-2-(5-(piperidin-4-yl)-1,2,4-oxadiazol-3-yl)-1,6-diaza-bicyclo[3.2.1]octan-6-yl hydrogen sulfate (9.0 mg). ESI-MS (EI+, m/z): 374.15 [M+H]+. 1H NMR (300 MHz, D2O) δ 4.61 (d, J=6.0 Hz, 1H), 4.12 (br s, 1H), 3.50-3.33 (m, 3H), 3.15-3.05 (m, 3H), 2.91 (d, J=12.2 Hz, 1H), 2.35-1.72 (m, 8H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:29]=[C:28]([O:30][CH3:31])[CH:27]=[CH:26][C:4]=1[CH2:5][N:6]([C:21]1[S:25][N:24]=[CH:23][N:22]=1)[S:7]([C:10]1[C:19]([F:20])=[CH:18][C:13]2[NH:14][C:15](=[O:17])[O:16][C:12]=2[CH:11]=1)(=[O:9])=[O:8].C(P(CCCC)CCCC)CCC.CCOC(/N=N/C(OCC)=O)=O.[I:57][C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][C:59]=1[C@@H:64](O)[CH3:65]>C1COCC1>[CH3:1][O:2][C:3]1[CH:29]=[C:28]([O:30][CH3:31])[CH:27]=[CH:26][C:4]=1[CH2:5][N:6]([C:21]1[S:25][N:24]=[CH:23][N:22]=1)[S:7]([C:10]1[C:19]([F:20])=[CH:18][C:13]2[N:14]([C@@H:64]([C:59]3[CH:60]=[CH:61][CH:62]=[CH:63][C:58]=3[I:57])[CH3:65])[C:15](=[O:17])[O:16][C:12]=2[CH:11]=1)(=[O:8])=[O:9]
Reactant: C[C@H](O)c1ccccc1I
Reactant: COc1ccc(CN(c2ncns2)S(=O)(=O)c2cc3oc(=O)[nH]c3cc2F)c(OC)c1
Agent: CCCCP(CCCC)CCCC
Agent: CCOC(=O)/N=N/C(=O)OCC
Solvent: C1CCOC1
Product: COc1ccc(CN(c2ncns2)S(=O)(=O)c2cc3oc(=O)n([C@H](C)c4ccccc4I)c3cc2F)c(OC)c1
Reaction time: 24 h

Procedure:
Added N-(2,4-dimethoxybenzyl)-5-fluoro-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (11-3, 2 g, 4.29 mmol) to THF (21.44 ml). Added tri-n-butylphosphine (2.116 ml, 8.58 mmol) and DEAD (1.358 ml, 8.58 mmol) and cooled to 0° C. Was a clear orange solution. Added (S)-1-(2-iodophenyl)ethanol (16-2, 1.064 g, 4.29 mmol). After 24 h at 0° C., concentrated in vacuo, dissolved in 5 mL DCM and purified by normal-phase HPLC (80 g ISCO column, 0-50% EtOAc:Hex) to give 32-1 as a white solid.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3](/[CH:7]=[CH:8]/[C:9]([OH:11])=O)[CH:2]=1.Cl.[CH3:13][N:14](C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.N1C=CC=C(/C=C/C(N[C:55]2[CH:60]=[CH:59][C:58]([S:61](=[O:75])(=[O:74])[NH:62][C:63]3[CH:68]=[CH:67][CH:66]=[CH:65][C:64]=3[O:69]C(F)(F)F)=[CH:57][CH:56]=2)=O)C=1>O1CCCC1>[CH:67]12[O:69][CH:64]([CH2:65][CH2:66]1)[CH2:63][N:62]([S:61]([C:58]1[CH:57]=[CH:56][C:55]([CH2:13][NH:14][C:9](=[O:11])/[CH:8]=[CH:7]/[C:3]3[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=3)=[CH:60][CH:59]=1)(=[O:74])=[O:75])[CH2:68]2
Reactant: CCN=C=NCCCN(C)C
Reactant: O=C(O)/C=C/c1cccnc1
Reactant: O=C(/C=C/c1cccnc1)Nc1ccc(S(=O)(=O)Nc2ccccc2OC(F)(F)F)cc1
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: O=C(/C=C/c1cccnc1)NCc1ccc(S(=O)(=O)N2CC3CCC(C2)O3)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 96.7 %

Procedure:
In a 25 mL round-bottomed flask was added (E)-3-(pyridin-3-yl)acrylic acid (38.0 mg, 0.255 mmol), N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (48.9 mg, 0.255 mmol) and 1-Hydroxybenzotriazole hydrate (39.0 mg, 0.255 mmol) in Tetrahydrofuran (Volume: 4 ml) to give a light yellow suspension. Diisopropylethylamine (0.089 ml, 0.510 mmol) and (4-(8-oxa-3-azabicyclo[3.2.1]octan-3-ylsulfonyl)phenyl)methanamine (48 mg, 0.170 mmol; prepared according to example 5) were added sequentially and the suspension was allowed to stir at room temperature overnight before being filtered through Celite®. The cake was washed with THF then the combined filtrate was concentrated in vacuo and the resulting residue was purified by Preparative-HPLC to afford the product (68.0 mg).
Reaction SMILES: C(=O)([O-])[O-].[Cs+].[Cs+].[OH:7][C:8]1[CH:40]=[CH:39][C:11]([CH2:12][CH:13]2[S:17][C:16](=[O:18])[N:15]([C:19]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:14]2=[O:38])=[CH:10][CH:9]=1.Br[CH2:42][C:43]([O:45][CH3:46])=[O:44]>CC(C)=O>[CH3:46][O:45][C:43]([CH2:42][O:7][C:8]1[CH:9]=[CH:10][C:11]([CH2:12][CH:13]2[S:17][C:16](=[O:18])[N:15]([C:19]([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:14]2=[O:38])=[CH:39][CH:40]=1)=[O:44]
Reactant: COC(=O)CBr
Reactant: O=C1SC(Cc2ccc(O)cc2)C(=O)N1C(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC(C)=O
Product: COC(=O)COc1ccc(CC2SC(=O)N(C(c3ccccc3)(c3ccccc3)c3ccccc3)C2=O)cc1
Reaction time: 1 h

Procedure:
126 g of cesium carbonate were added at room temperature to a solution of 120 g of 5-(4-hydroxybenzyl)-3-triphenylmethylthiazolidine-2,4-dione in 2.5 liters of acetone, followed by 36 ml of methyl bromoacetate, and the resulting mixture was stirred for 1 hour. At the end of this time, the reaction mixture was freed from the solvent by distillation under reduced pressure, and the resulting residue was mixed with water. The aqueous mixture was then extracted with ethyl acetate. The extract was washed with water and then with a saturated aqueous solution of sodium chloride, after which it was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, after which 1 liter of diethyl ether was added to the oily residue. The mixture was then agitated ultrasonically for 10 minutes. The solid substance precipitated was collected by filtration, to give 126.3 g of the title compound, melting at 158°-162° C.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][NH:10][C:11]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:4][CH:3]=1.C([Li])CCC.[CH2:35]([O:42][C@@H:43]1[C@@H:49]([O:50][CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[C@H:48]([O:58][CH2:59][C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)[C@@H:47]([CH2:66][O:67][CH2:68][C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=2)[O:46][C:44]1([C:75]1[CH:80]=[C:79]([CH:81]=[O:82])[C:78]([CH3:83])=[CH:77][C:76]=1[O:84][CH2:85][C:86]1[CH:91]=[CH:90][CH:89]=[CH:88][CH:87]=1)[OH:45])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>O.O1CCCC1.CCCCCC>[CH2:35]([O:42][C@@H:43]1[C@@H:49]([O:50][CH2:51][C:52]2[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=2)[C@H:48]([O:58][CH2:59][C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)[C@@H:47]([CH2:66][O:67][CH2:68][C:69]2[CH:70]=[CH:71][CH:72]=[CH:73][CH:74]=2)[O:46][C:44]1([C:75]1[CH:80]=[C:79]([CH:81]([OH:82])[C:2]2[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][NH:10][C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:6][CH:7]=2)[C:78]([CH3:83])=[CH:77][C:76]=1[O:84][CH2:85][C:86]1[CH:87]=[CH:88][CH:89]=[CH:90][CH:91]=1)[OH:45])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1
Reactant: Cc1cc(OCc2ccccc2)c(C2(O)O[C@H](COCc3ccccc3)[C@@H](OCc3ccccc3)[C@H](OCc3ccccc3)[C@H]2OCc2ccccc2)cc1C=O
Reactant: Brc1ccc(CCNC(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: O
Solvent: C1CCOC1
Product: Cc1cc(OCc2ccccc2)c(C2(O)O[C@H](COCc3ccccc3)[C@@H](OCc3ccccc3)[C@H](OCc3ccccc3)[C@H]2OCc2ccccc2)cc1C(O)c1ccc(CCNC(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Reaction time: 0.5 h
Yield: 64.1 %

Procedure:
To a tetrahydrofuran solution (3 mL) of 2-(4-bromophenyl)-N-tritylethaneamine (0.814 g, 1.84 mmol) was added dropwise under nitrogen atmosphere at −78° C. a 2.66 M hexane solution of n-butyllithium (0.69 mL, 1.84 mmol), and the mixture was stirred for 30 minutes at the same temperature. Then a tetrahydrofuran solution (3 mL) of 2,3,4,6-tetra-O-benzyl-1-C-[2-(benzyloxy)-5-formyl-4-methylphenyl]-D-glucopyranose (0.670 g, 0.876 mmol) was added dropwise, and the mixture was stirred for 30 minutes at the same temperature. To the reaction solution was added water, and the resulting mixture was extracted with ethyl acetate. The organic layer was dried with anhydrous magnesium sulfate. The drying agent was filtered off, and the solvent was evaporated under reduced pressure. Thus obtained residue was purified with NH type silica gel column chromatography (chloroform) to obtain the title compound (0.634 g, 64%) as a yellow oily compound.