Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([Si:5]([CH3:20])([CH3:19])[O:6][CH2:7][CH2:8][C:9]([CH3:18])([CH3:17])[CH2:10][CH2:11]OS(C)(=O)=O)([CH3:4])([CH3:3])[CH3:2].[N-:21]=[N+:22]=[N-:23].[Na+].O>CN(C)C=O>[N:21]([CH2:11][CH2:10][C:9]([CH3:18])([CH3:17])[CH2:8][CH2:7][O:6][Si:5]([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:20])[CH3:19])=[N+:22]=[N-:23]
Reactant: CC(C)(CCO[Si](C)(C)C(C)(C)C)CCOS(C)(=O)=O
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(CCN=[N+]=[N-])CCO[Si](C)(C)C(C)(C)C
Temperature: 60 °C
Yield: 59.4 %

Procedure:
Step B To the solution of methanesulfonic acid 5-(tert-butyl-dimethyl-silanyloxy)-3,3-dimethyl-pentyl ester (1.48 g, 4.96 mmol) in anhydrous dimethylformamide (10 mL) was added NaN3 (1.6 g, 25 mmol). The reaction mixture was heated at 60° C. for 18 h. The mixture was cooled, and water was added. The mixture was extracted with ethyl acetate twice. The combined organic layers were washed with saturated aqueous NaHCO3 solution, brine, dried over MgSO4 to give (5-azido-3,3-dimethyl-pentyloxy)-tert-butyl-dimethyl-silane as a yellow oil (0.8 g, 67%).
Reaction SMILES: O=[C:2]1[CH2:8][C@H:7]2[N:4]([C:5](=[O:26])[C@@H:6]2[C:9]([CH3:25])([O:11][C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=2)=[O:13])[CH3:10])[C@H:3]1[C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][C:34]([N+:37]([O-:39])=[O:38])=[CH:33][CH:32]=1)=[O:28].C(N(C(C)C)CC)(C)C.C1(OP(Cl)(OC2C=CC=CC=2)=O)C=CC=CC=1.[SH:66][C:67]1[CH:72]=[CH:71][N:70]=[CH:69][CH:68]=1>CN(C1C=CN=CC=1)C.C(#N)C.C(OCC)(=O)C>[N:70]1[CH:71]=[CH:72][C:67]([S:66][C:2]2[CH2:8][C@H:7]3[N:4]([C:5](=[O:26])[C@@H:6]3[C:9]([CH3:25])([O:11][C:12]([O:14][CH2:15][C:16]3[CH:17]=[CH:18][C:19]([N+:22]([O-:24])=[O:23])=[CH:20][CH:21]=3)=[O:13])[CH3:10])[C:3]=2[C:27]([O:29][CH2:30][C:31]2[CH:32]=[CH:33][C:34]([N+:37]([O-:39])=[O:38])=[CH:35][CH:36]=2)=[O:28])=[CH:68][CH:69]=1
Reactant: Sc1ccncc1
Reactant: CC(C)(OC(=O)OCc1ccc([N+](=O)[O-])cc1)[C@H]1C(=O)N2[C@@H](C(=O)OCc3ccc([N+](=O)[O-])cc3)C(=O)C[C@H]12
Agent: CN(C)c1ccncc1
Agent: O=P(Cl)(Oc1ccccc1)Oc1ccccc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CC(C)(OC(=O)OCc1ccc([N+](=O)[O-])cc1)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(Sc3ccncc3)C[C@H]12
Temperature: 0 °C
Reaction time: 8 h
Yield: 81.8 %

Procedure:
To a solution of 4-nitrobenzyl(2R,5R,6S)-3,7-dioxo-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-1-azabicyclo[3.2.0]heptane-2-carboxylate (145.1 mg) and 4-(N,N-dimethylamino)pyridine (3.27 mg) in acetonitrile (7.3 ml) was added dropwise a solution of N,N-diisopropyl-N-ethylamine (56.0 μl) in acetonitrile (0.504 μl), followed by a solution of diphenyl-chlorophosphate (58.3 μl) in acetonitrile (0.525 ml) at 0° C. After stirring for an hour at 0° C., thereto was added a solution of N,N-diisopropyl-N-ethylamine (186.4 μl) in acetonitrile (1.68 ml), followed by 4-mercaptopyridine (31.3 mg) at -15° C. The mixture was allowed to stand overnight at -15° C. The resultant solution was diluted with ethyl acetate (15 ml) and then washed in turn with water and saturated aqueous sodium chloride. After drying over magnesium sulfate, the solution was filtered and evaporated in vacuo. The residue was chromatographed on silica gel (4 g) eluting with a mixture of benzene and acetone (30:1 to 6:1) to give 4-nitrobenzyl(5R,6S)-3-(4-pyridylthio)-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (139.1 mg).
Reaction SMILES: C(O[C:4]1[CH2:8][CH:7]([S:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[CH2:6][N:5]=1)C.[CH:19]([NH:21][NH2:22])=O.C(O)(=O)C.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.C(OCC)(=O)C>[CH3:18][O:17][C:14]1[CH:13]=[CH:12][C:11]([CH2:10][S:9][CH:7]2[CH2:6][N:5]3[C:4](=[N:22][N:21]=[CH:19]3)[CH2:8]2)=[CH:16][CH:15]=1
Reactant: CCOC1=NCC(SCc2ccc(OC)cc2)C1
Reactant: NNC=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: COc1ccc(CSC2Cc3nncn3C2)cc1
Temperature: 80 °C
Reaction time: 1.5 h

Procedure:
To a solution of 2-ethoxy-4-p-methoxybenzylthio-1-pyrroline (1.06 g) in ethanol (50 ml) there was added 0.36 g of formylhydrazine and heated to 80° C. under argon atmosphere while stirring. After 1.5 hours, 0.24 g of formylhydrazine was further added and stirred under heating for 30 minutes at the same temperature. Then, 0.6 g of acetic acid was added, stirred for 30 minutes at that temperature and then cooled to room temperature. To the cooled product were added ethyl acetate and 5% aqueous solution of sodium carbonate to distribute the product between these two liquids. The resulting organic phase was washed with saturated NaCl aqueous solution, dried over Na2SO4 and distilled off the solvent under reduced pressure to obtain the objective product.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:33](O)=[O:34])[C:10]([S:13][C:14]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([CH3:12])[CH3:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C.Cl.[CH2:58]([O:60][C:61](=[O:64])[CH2:62][NH2:63])[CH3:59]>C(Cl)(Cl)Cl.O1CCCC1.O.C(N(CC)CC)C>[CH2:58]([O:60][C:61](=[O:64])[CH2:62][NH:63][C:33](=[O:34])[C@H:9]([C:10]([S:13][C:14]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)([CH3:12])[CH3:11])[NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH3:59]
Reactant: CC(C)(C)OC(=O)N[C@H](C(=O)O)C(C)(C)SC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CCOC(=O)CN
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Solvent: O
Product: CCOC(=O)CNC(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)SC(c1ccccc1)(c1ccccc1)c1ccccc1
Reaction time: 1 h
Yield: 99 %

Procedure:
To the solution of N-t-butoxycarbonyl-S-trityl-L-penicillamine (A-1) (4.0 g) and 1-hydroxybenzotriazole (abbreviated as HOBt) (1.2 g) in chloroform (40 ml) and tetrahydrofuran (16 ml), was added dropwise by ice-cooling the solution of 1-ethyl-3-(3dimethylaminopropyl)carbodiimide (water-soluble carbodiimide: abbreviated as WSC) (1.7 g) in chloroform (10 ml). The mixture was stirred at the same temperature for 1 hour, then glycine ethyl ester hydrochloride (1.1 g) and triethylamine (0.85 ml) were added, and the mixture was stirred at room temperature for 12 hours. After addition of water, the organic layer was washed with an aqueous solution of potassium hydrogensulfate, water, an aqueous solution of sodium hydrogencarbonate, water and saturated saline, in this order, and dried over magnesium sulfate. The solvent was evaporated off under reduced pressure, and the residue was subjected to column chromatography, to give N-t-butoxycarbonyl-S-trityl-L-penicillamylglycine ethyl ester (4.5 g).
Reaction SMILES: [Cl:1][C:2]1[C:3]([NH:17][CH2:18][C:19]([CH:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)=O)=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][C:8]([C:12]([O:14][CH3:15])=[O:13])=[C:7]([CH3:16])[CH:6]=2.FC(F)(F)C(OC(=O)C(F)(F)F)=O.FC(F)(F)C(O)=O.C(=O)([O-])O.[Na+]>C(OCC)(=O)C.C(Cl)(Cl)Cl>[Cl:1][C:2]1[C:3]2[N:4]([C:19]([CH:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)=[CH:18][N:17]=2)[C:5]2[C:10]([N:11]=1)=[CH:9][C:8]([C:12]([O:14][CH3:15])=[O:13])=[C:7]([CH3:16])[CH:6]=2
Reactant: COC(=O)c1cc2nc(Cl)c(NCC(=O)C3CCCC3)nc2cc1C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: ClC(Cl)Cl
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)c1cc2nc(Cl)c3ncc(C4CCCC4)n3c2cc1C
Yield: 78.5 %

Procedure:
To a mixed liquid of 520 mg of methyl 3-chloro-2-[(2-cyclopentyl-2-oxoethyl)amino]-7-methylquinoxaline-6-carboxylate and 11.3 mL of chloroform were added 4.00 mL of trifluoroacetic anhydride and 0.11 mL of trifluoroacetic acid, followed by heating and refluxing for 6 hours. Ethyl acetate and a saturated aqueous sodium hydrogen carbonate solution were added thereto, followed by extraction with ethyl acetate, the organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol) to obtain 388 mg of methyl 4-chloro-1-cyclopentyl-8-methylimidazo[1,2-a]quinoxaline-7-carboxylate as a pale yellow solid.
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][CH:13]=1)[O:6][CH:7]1[CH2:10][NH:9][CH2:8]1.C1(CC2C=CC=CC=2)C=CC=CC=1.[CH2:29]([N:32]=[C:33]=[O:34])[CH:30]=[CH2:31]>C(OC(C)C)(C)C>[CH2:29]([NH:32][C:33]([N:9]1[CH2:10][CH:7]([O:6][C:5]2[CH:11]=[CH:12][CH:13]=[C:3]([C:2]([F:1])([F:14])[F:15])[CH:4]=2)[CH2:8]1)=[O:34])[CH:30]=[CH2:31]
Reactant: FC(F)(F)c1cccc(OC2CNC2)c1
Reactant: C=CCN=C=O
Solvent: CC(C)OC(C)C
Solvent: c1ccc(Cc2ccccc2)cc1
Product: C=CCNC(=O)N1CC(Oc2cccc(C(F)(F)F)c2)C1
Reaction time: 1 h
Yield: 63.3 %

Procedure:
A solution of 18.9 g (0.05 mole) of crude 3-[3-(trifluoromethyl)phenoxy]azetidine (contains an equal molar amount of diphenylmethane) in 100 ml of isopropyl ether was stirred under nitrogen while 4.16 g (0.05 mole) of 2-propenyl isocyanate was slowly added. The reaction mixture which was somewhat turbid, cleared and after 1 hr a fine crystalline precipitate began to form. After stirring for 18 hrs, the product was removed by filtration, washed with fresh isopropyl ether and air dried to yield 9.5 g of white crystals, m.p. 75°-76° C.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].Cl[CH2:8][C:9]1[NH:10][C:11]2[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=2[N:13]=1.[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([N:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)=[CH:22][CH:21]=1>CN(C=O)C.O>[CH3:18][O:19][C:20]1[CH:21]=[CH:22][C:23]([N:26]2[CH2:31][CH2:30][N:29]([CH2:8][C:9]3[NH:10][C:11]4[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=4[N:13]=3)[CH2:28][CH2:27]2)=[CH:24][CH:25]=1
Reactant: COc1ccc(N2CCNCC2)cc1
Reactant: ClCc1nc2ccccc2[nH]1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccc(N2CCN(Cc3nc4ccccc4[nH]3)CC2)cc1
Reaction time: 8 h

Procedure:
Potassium carbonate (2.76 g, 20 mmol) and 2-(chloromethyl)benzimidazole (1.70 g, 10 mmol) were added to a solution of 1-(4-methoxyphenyl)piperazine (1.92 g, 10 mmol) in DMF (20 ml) under a nitrogen atmosphere and the mixture was stirred overnight. The mixture was diluted with water (200 ml) and extracted with ethyl acetate (3×100 ml). The combined organic layers were washed with water (100 ml) and brine (100 ml), dried (MgSO4) and evaporated in vacuo to give a solid which was recrystallised from toluene to give the title compound as a buff solid (731 mg, 23%). mp 214°-216° C.; (Found: C, 70.80; H, 6.82; N, 17.28. C19H22N4O requires C, 70.78; H, 6.88; N, 17.38%); δH (DMSO-d6) 2.59-2.62 (4H, m, 2×piperazinyl CH2), 3.03-3.05 (4H, m, 2×piperazinyl CH2), 3.67 (3H, s, OCH3), 3.77 (2H, s, CH2N), 6.79-6.82 (2H, m, ArH), 6.85-6.89 (2H, m, ArH), 7.10-7.17 (2H, m, ArH), 7.43 (1H, d, J 6.9 Hz, ArH), 7.55 (1H, d, J 6.9 Hz, ArH), and 12.30 (1H, brs, NH); m/z (CI+, NH3) 323 (M+1)+.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([C:11]([F:14])([F:13])[F:12])[CH:3]=1.CO.[CH3:17][Si](C=[N+]=[N-])(C)C>C1COCC1>[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([O:8][CH3:17])=[O:7])=[C:4]([C:11]([F:12])([F:13])[F:14])[CH:3]=1
Reactant: C[Si](C)(C)C=[N+]=[N-]
Reactant: Nc1ccc(C(=O)O)c(C(F)(F)F)c1
Solvent: C1CCOC1
Solvent: CO
Product: COC(=O)c1ccc(N)cc1C(F)(F)F
Reaction time: 0.08 h

Procedure:
4-Amino-2-(trifluoromethyl)benzoic acid (10 g, 48.8 mmol) was suspended in THF (100 mL) and methanol (30 mL) and was cooled in an ice bath. (Trimethylsilyl)diazomethane (2 M solution in hexanes; 32 mL) was added drop-wise. The mixture was stirred for 5 minutes and then concentrated to afford methyl 4-amino-2-(trifluoromethyl)benzoate (quantitative yield) as a brown oil. 1H NMR (400 MHz, CDCl3): δ 7.78 (d, 1H), 6.99 (d, 1H), 6.77 (d, 1H), 4.18 (br s, 2H), 3.88 (s, 3H); GCMS for C9H8F3NO2: 219 (M+).
Reaction SMILES: [Li+].[OH-].CC1C(C([O:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]34[N:37]([C:38]([C:40]5[C:41]([CH3:45])=[N:42][O:43][CH:44]=5)=[O:39])[CH2:36][CH2:35][N:20]3[C:21](=[O:34])[C:22]3[N:23]([CH:25]=[C:26]([C:28]5[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=5)[CH:27]=3)[CH2:24]4)=[CH:15][CH:14]=2)=O)=CON=1.CO.CC#N>[Cl-].[Na+].O>[OH:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]23[N:37]([C:38]([C:40]4[C:41]([CH3:45])=[N:42][O:43][CH:44]=4)=[O:39])[CH2:36][CH2:35][N:20]2[C:21](=[O:34])[C:22]2[N:23]([CH:25]=[C:26]([C:28]4[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=4)[CH:27]=2)[CH2:24]3)=[CH:15][CH:14]=1
Reactant: Cc1nocc1C(=O)OCc1ccc(C23Cn4cc(-c5cccnc5)cc4C(=O)N2CCN3C(=O)c2conc2C)cc1
Agent: [Cl-]
Agent: [Li+]
Agent: [Na+]
Solvent: CC#N
Solvent: CO
Solvent: O
Product: Cc1nocc1C(=O)N1CCN2C(=O)c3cc(-c4cccnc4)cn3CC12c1ccc(CO)cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Aqueous LiOH solution (1M)(0.75 mg, 0.018 mmol) was added to a solution of 4-{1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-5-oxo-7-(pyridin-3-yl)-2,3-dihydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]-pyrazin-10a(10H)-yl}benzyl 3-methyl-1,2-oxazole-4-carboxylate (9.6 mg, 0.016 mmol) in a mixture MeOH/CH3CN (2 mL) and stirred at room temperature for 3 h. Brine (1 mL) was added and the resultant mixture was extracted with EtOAc (3×1 mL). The organic layers were combined, dried (MgSO4) and concentrated in vacuo to give a residue that was purified by flash chromatography (Biotage SP4 gradient 0-10% MeOH in EtOAc, 10CV and hold 10CV). The compound 10a-[4-(hydroxymethyl)phenyl]-1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-7-(pyridin-3-yl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (95) was isolated as a white solid (2.8 mg, yield 37%).
Reaction SMILES: [O:1]=[C:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:12]=[C:11]([CH2:13][NH:14][C:15]2[CH:23]=[CH:22][CH:21]=[CH:20][C:16]=2[C:17]([OH:19])=O)[CH:10]=[CH:9][N:8]=1.[NH2:24][C:25]1[CH:26]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:29][CH:30]=1.CN1CCOCC1>CN(C)C=O.C(OCC)(=O)C>[O:1]=[C:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:12]=[C:11]([CH2:13][NH:14][C:15]2[CH:23]=[CH:22][CH:21]=[CH:20][C:16]=2[C:17]([NH:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:32])([F:33])[F:34])[CH:26]=2)=[O:19])[CH:10]=[CH:9][N:8]=1
Reactant: Nc1cccc(C(F)(F)F)c1
Reactant: O=C(O)c1ccccc1NCc1ccnc(N2CCCC2=O)c1
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Solvent: CCOC(C)=O
Product: O=C(Nc1cccc(C(F)(F)F)c1)c1ccccc1NCc1ccnc(N2CCCC2=O)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 41.8 %

Procedure:
156 mg (0.5 mmol) of 2-{[2-(2-oxo-pyrrolidin-1-yl)-pyridin-4-ylmethyl]-amino}-benzoic acid is mixed in 5 ml of dimethylformamide with 0.12 ml (1 mmol) of 3-aminobenzotrifluoride, 228 mg (0.6 mmol) of HATU (N-dimethylamino-1H-1,2,3-triazolo-[4,5-b]pyridin-1-ylmethylene]-N-methylmethanammoniumhexafluorophosphate-N-oxide) and 0.14 ml of N-methylmorpholine, and it is stirred overnight at room temperature. It is diluted with ethyl acetate and washed in succession with saturated sodium bicarbonate solution, water and saturated common salt solution. The organic phase is dried, filtered and concentrated by evaporation. The residue is chromatographed on Isolute as a mobile solvent. 95 mg (42% of theory) of 2-{[2-(2-oxo-pyrrolidin-1-yl)-pyridin-4-ylmethyl]-amino}-N-(3-trifluoromethyl-phenyl)-benzamide is obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:22]=[C:21]([S:23]([CH3:26])(=[O:25])=[O:24])[CH:20]=[CH:19][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]([CH3:18])[S:16][CH:17]=2)=[CH:9][CH:8]=1)=[O:5].[C:27](O[K])(C)(C)C.CI>C1COCC1.CC(O)(C)C>[Cl:1][C:2]1[CH:22]=[C:21]([S:23]([CH3:26])(=[O:24])=[O:25])[CH:20]=[CH:19][C:3]=1[C:4]([N:6]([CH3:27])[C:7]1[CH:8]=[CH:9][C:10]([C:13]2[N:14]=[C:15]([CH3:18])[S:16][CH:17]=2)=[CH:11][CH:12]=1)=[O:5]
Reactant: Cc1nc(-c2ccc(NC(=O)c3ccc(S(C)(=O)=O)cc3Cl)cc2)cs1
Reactant: CC(C)(C)O[K]
Solvent: CC(C)(C)O
Solvent: CI
Solvent: C1CCOC1
Product: Cc1nc(-c2ccc(N(C)C(=O)c3ccc(S(C)(=O)=O)cc3Cl)cc2)cs1
Reaction time: 0.25 h
Yield: 77 %

Procedure:
To a stirring solution of 2-chloro-4-(methylsulfonyl)-N-(4-(2-methylthiazol-4-yl)phenyl)benzamide (50 mg, 0.123 mmol) in THF (1 mL) under nitrogen atmosphere was added 1M solution of tBuOK in tBuOH (0.14 mL) dropwise. After stirring for 15 min, CH3I (0.009 mL, 0.14 mmol) was added and the reaction mixture was stirred at 60° C. for 1 h, before partitioning between water and EtOAc. The organic layer was isolated, washed with brine, and adsorbed on silica. Purification on silica by flash chromatography using a gradient of 40-100% EtOAc/hexane yielded 40 mg of the titled compound as an off-white solid (77% yield).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH3:13])[CH3:12])(=[O:10])=[O:9])=[C:4]([C:14]([F:17])([F:16])[F:15])[CH:3]=1.[C:18]([C:20]1[N:24]([CH3:25])[C:23](B(O)O)=[CH:22][CH:21]=1)#[N:19].[F-].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[C:18]([C:20]1[N:24]([CH3:25])[C:23]([C:2]2[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH3:13])[CH3:12])(=[O:10])=[O:9])=[C:4]([C:14]([F:17])([F:16])[F:15])[CH:3]=2)=[CH:22][CH:21]=1)#[N:19]
Reactant: Cn1c(C#N)ccc1B(O)O
Reactant: CN(C)S(=O)(=O)c1ccc(Br)cc1C(F)(F)F
Agent: [Pd]
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Product: CN(C)S(=O)(=O)c1ccc(-c2ccc(C#N)n2C)cc1C(F)(F)F
Reaction time: 16 h
Yield: 57.5 %

Procedure:
According to general procedure B, 4-bromo-N,N-dimethyl-2-(trifluoromethyl)benzenesulfonamide (186 mg, 0.56 mmol), 5-cyano-1-methyl-1H-pyrrol-2-ylboronic acid (100 mg, 0.67 mmol), potassium fluoride (107 mg, 1.85 mmol), and tris(dibenzylideneacetone)dipalladium(0) (14 mg, 0.01 mmol) were placed in an oven dried flask under nitrogen and dry THF (1.4 mL) was added. Tri-t-butylphosphine (83 μL, 0.02 mmol, 10 wt % in hexane) was added and the reaction was stirred for 16 hours. 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N,N-dimethyl-2-(trifluoromethyl)benzenesulfonamide (115 mg, 58%) was provided after purification. MS (ESI) m/z 357. HPLC purity 98.4% at 210-370 nm, 10.4 min.; the Xterra® RP18 column, 3.5μ, 150×4.6 mm column, 1.2 mL/min., 85/15-5/95 (ammonium formate buffer pH=3.5/ACN+MeOH) for 10 min., hold 4 min.
Reaction SMILES: [Cl:1]Cl.[Cl:3][CH2:4][C:5]([F:11])([F:10])[C:6]([F:9])([F:8])[F:7]>>[Cl:3][CH:4]([Cl:1])[C:5]([F:11])([F:10])[C:6]([F:9])([F:8])[F:7]
Reactant: ClCl
Reactant: FC(F)(F)C(F)(F)CCl
Product: FC(F)(F)C(F)(F)C(Cl)Cl

Procedure:
Until HCFC-225ca becomes available in commercial quantities, HCFC-225ca may be prepared by a standard and well-known organic synthesis technique. For example, to prepare 1,1-dichloro-2,2,3,3,3-pentafluoropropane, 2,2,3,3,3-pentafluoro-1-propanol and p-toluenesulfonate chloride are reacted together to form 2,2,3,3,3-pentafluoropropyl-p-toluenesulfonate. Then, N-methylpyrrolidone, lithium chloride, and the 2,2,3,3,3-pentafluoropropyl-p-toluenesulfonate are reacted together to form 1-chloro-2,2,3,3,3-pentafluoropropane. Chlorine and the 1-chloro-2,2,3,3,3-pentafluoropropane are then reacted together to form 1,1-dichloro-2,2,3,3,3-pentafluoropropane. A detailed synthesis is set forth below.
Reaction SMILES: [CH2:1]([N:8]1[C:12]([CH3:13])=[C:11]([CH:14]2[S:19][CH2:18][C:17](=O)[CH2:16][S:15]2)[N:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(=O)C.[Na+].Cl.[NH2:27][OH:28]>CO.O.C(Cl)(Cl)Cl>[CH2:1]([N:8]1[C:12]([CH3:13])=[C:11]([CH:14]2[S:19][CH2:18][C:17](=[N:27][OH:28])[CH2:16][S:15]2)[N:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1c(C2SCC(=O)CS2)ncn1Cc1ccccc1
Reactant: NO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Solvent: ClC(Cl)Cl
Solvent: O
Product: Cc1c(C2SCC(=NO)CS2)ncn1Cc1ccccc1
Temperature: 25 °C
Reaction time: 5 h
Yield: 94.4 %

Procedure:
To a solution of 2-(1-benzyl-5-methyl-4-imidazolyl)-1,3-dithian-5-one (11.2 g., 0.0368 mole) in methanol (50 ml.) and water (20 ml.) is added sodium acetate (3.1 g.) and hydroxylamine hydrochloride (2.6 g., 0.037 mole). The reaction is stirred at ambient temperature for 5 hours. The mixture is diluted with chloroform, washed with water, dried and evaporated to give a solid crude product (11.1 g.), 2-(1-benzyl-5-methyl-4-imidazolyl)-1,3-dithian-5-one oxime, which is used as is in the following steps.
Reaction SMILES: Br.[C:2]([N:5]1[CH2:10][CH2:9][C:8](=O)[CH:7](Br)[CH2:6]1)(=[O:4])[CH3:3].C(N(CC)CC)C.[C:20]([NH2:23])(=[S:22])[CH3:21]>CC(C)=O>[C:2]([N:5]1[CH2:10][CH2:9][C:8]2[N:23]=[C:20]([CH3:21])[S:22][C:7]=2[CH2:6]1)(=[O:4])[CH3:3]
Reactant: CC(N)=S
Reactant: CC(=O)N1CCC(=O)C(Br)C1
Agent: Br
Solvent: CCN(CC)CC
Solvent: CC(C)=O
Product: CC(=O)N1CCc2nc(C)sc2C1

Procedure:
N-Acetyl-3-bromo-4-piperidone hydrobromide (5.0 g, 16.6 mmol) in acetone (160 ml) was heated to 60° and treated with triethylamine (2.31 ml, 33.1 mmol) and thioacetamide (1.24 g, 16.6 mmol). The reaction mixture was heated to reflux for 24 hours, then cooled and filtered, to provide a yellow solid which was purified by column chromatography (eluant: 89:10:1 chloroform: methanol: concentrated aqueous ammonium hydroxide). The title product was obtained as a yellow oil (995 mg, 5.1 mmol, 31% yield).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:19])[CH2:15][C:16](=[O:18])[CH3:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(C1C=CC(S([N:41]=[N+:42]=[N-])(=O)=O)=CC=1)CCCCCCCCCCC.C(N(CC)CC)C.CCOCC>CC#N>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:19])[C:15](=[N+:41]=[N-:42])[C:16](=[O:18])[CH3:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(=O)CC(=O)C1CCN(C(=O)OC(C)(C)C)CC1
Reactant: CCCCCCCCCCCCc1ccc(S(=O)(=O)N=[N+]=[N-])cc1
Solvent: CCOCC
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CC(=O)C(=[N+]=[N-])C(=O)C1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 4.5 h

Procedure:
A solution of 0.51 g (1.8 mmol) of 1-(tert-butoxycarbonyl)-4-(1,3-dioxo-but-1-yl)piperidine (from Step B) and 0.65 g (1.8 mmol) of para-dodecylbenzenesulfonyl azide (Syn. Comm. 1981, 11, 947–956) in CH3CN at 0° C. was treated with 0.26 mL (1.8 mmol) of triethylamine. The reaction was warmed to rt and stirred for 4.5 hours. The reaction was poured into 100 mL of Et2O and washed with 100 mL of H2O, 100 mL of 2 N HCl and 100 mL of brine. The organic layer was dried over MgSO4 and concentrated. The residue was purified with a 40M Biotage column using 9:1 v/v of hexanes/acetone to afford the title compound as a light yellow oil: RF: 0.33 (4:1 v/v hexanes/acetone); 1H-NMR (500 MHz) δ 1.46 (s, 9H), 1.57–1.76 (m, 4H), 2.42 (s, 3H), 2.82 (m, 2H), 3.24 (m, 1H), 4.14 (m, 2H).
Reaction SMILES: [CH:1]1([N:7]([CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:8](=[O:20])[NH:9][C:10]2[S:11][C:12]([S:15][CH2:16][C:17]([OH:19])=[O:18])=[CH:13][N:14]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C1(=O)CCCCC1>C(OC(=O)C)C>[CH:23]12[CH2:28][CH:27]([CH:25]=[CH:24]1)[CH2:26][CH:22]2[CH2:21][N:7]([CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)[C:8](=[O:20])[NH:9][C:10]1[S:11][C:12]([S:15][CH2:16][C:17]([OH:19])=[O:18])=[CH:13][N:14]=1
Reactant: O=C(O)CSc1cnc(NC(=O)N(CCc2ccccc2)C2CCCCC2)s1
Solvent: CCOC(C)=O
Solvent: O=C1CCCCC1
Product: O=C(O)CSc1cnc(NC(=O)N(CC2CC3C=CC2C3)C2CCCCC2)s1

Procedure:
Prepared as described for the synthesis of [2-(3-cyclohexyl-3-phenethyl-ureido)-thiazol-5-ylsulfanyl]-acetic acid, from c-bicyclo[2.2.1]hept-5-en-2-yl-methylamine, cyclohexanone and 2-amino-thiazol-5-ylsulfanyl)-acetic acid ethyl ester.