Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:10]=[CH:9][N:8]2[CH:11]=[CH:12][N:13]=[C:7]2[N:6]=1)=O.[OH-].[NH4+:15]>>[N:13]1[CH:12]=[CH:11][N:8]2[CH:9]=[CH:10][C:5]([C:3]([NH2:15])=[O:2])=[N:6][C:7]=12
Reactant: COC(=O)c1ccn2ccnc2n1
Reactant: [NH4+]
Agent: [OH-]
Product: NC(=O)c1ccn2ccnc2n1
Temperature: 100 °C
Yield: 58 %

Procedure:
A mixture of imidazo[1,2-α]pyrimidine-7-carboxylic acid methyl ester (580 mg) and 28% ammonium hydroxide was heated at 100° C. in a sealed tube for 2 h then cooled to ambient temperature. The resulting solid was filtered, washed with ice-cold water and dried under vacuum to give imidazo[1,2-α]pyrimidine-7-carboxylic acid amide (310 mg, 58%) as a white solid: δH (360 MHz, DMSO) 7.61 (1H, d, J 7), 7.77 (1H, s), 7.92 (1H, d, J 1), 8.09 (1H, d, J 1), 8.32 (1H, s), 9.11 (1H, d, J 7).
Reaction SMILES: [N:1]1([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[P:12]2[C:17]([CH3:19])([CH3:18])[CH2:16][C:15](=O)[CH2:14][C:13]2([CH3:22])[CH3:21])[CH:5]=[CH:4][CH:3]=[CH:2]1.C(O)COCCO.O.NN.[OH-].[K+]>O.C(OCC)(=O)C>[CH3:21][C:13]1([CH3:22])[CH2:14][CH2:15][CH2:16][C:17]([CH3:18])([CH3:19])[P:12]1[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=1[N:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1
Reactant: CC1(C)CC(=O)CC(C)(C)P1c1ccccc1-n1cccc1
Agent: NN
Agent: [K+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: O
Solvent: OCCOCCO
Product: CC1(C)CCCC(C)(C)P1c1ccccc1-n1cccc1
Temperature: 210 °C
Reaction time: 7 h
Yield: 96.7 %

Procedure:
A round bottom flask was charged with 1-(2-(1H-pyrrol-1-yl)phenyl)-2,2,6,6-tetramethylphosphinan-4-one (878 mg, 2.80 mmol, 1.0 equiv) and purged with nitrogen for 15 minutes. Then nitrogen-sparged diethylene glycol (14.7 mL, 154 mmol, 55 equiv) was added and the flask was equipped with a Claisen adapter and a Dean-Stark trap. The flask was further charged with hydrazine hydrate (1.24 mL, 14.0 mmol, 5 equiv, 55 wt % hydrazine) and potassium hydroxide (786 mg, 14.0 mmol, 5 equiv), and the mixture was immersed in an oil bath at 60° C. The temperature of the bath was gradually increased to 210° C. over 1 hour and kept at that temperature for 7 hours. The reaction mixture was cooled to room temperature under a positive pressure of nitrogen and then diluted with water (50 mL) and ethyl acetate (20 mL). The phases were partitioned, and the organic layer was collected. The aqueous layer was washed with ethyl acetate (4×20 mL), and the combined organic fractions were washed once with aqueous saturated sodium chloride, dried over sodium sulfate, filtered, and concentrated on a rotary evaporator to afford the title compound as a pale yellow solid (811 mg, 91 area % by HPLC, 97% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.96-7.83 (m, 1H), 7.35-7.22 (m, 2H), 7.22-7.17 (m, 1H), 6.72-6.66 (m, 2H), 6.20 (t, J=2.1 Hz, 2H), 1.87-1.71 (m, 2H), 1.71-1.56 (m, 2H), 1.50-1.33 (m, 2H), 1.11 (s, 3H), 1.06 (s, 3H), 0.76 d, J=9.7 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ ppm 149.4-146.8 (m), 134.7 (d, J=4 Hz) 129.0, 127.8 (d, J=3 Hz), 126.5, 123.3 (d, J=3 Hz), 107.9, 37.6, 31.4, 31.1, 30.2 (d, J=7 Hz), 29.6 (d, J=18 Hz), 20.5. 31P NMR (CDCl3, 202 MHz) δ ppm −7.6 (s).
Reaction SMILES: [CH3:1][C:2]1([CH3:16])[S:6][C:5]2=[CH:7][C:8]3[S:9][C:10]([CH3:15])([CH3:14])[O:11][C:12]=3[CH:13]=[C:4]2[O:3]1.C([Li])CCC.Cl[Si:23]([CH3:26])([CH3:25])[CH3:24]>C1COCC1>[CH3:24][Si:23]([CH3:26])([CH3:25])[C:13]1[C:4]2[O:3][C:2]([CH3:16])([CH3:1])[S:6][C:5]=2[CH:7]=[C:8]2[S:9][C:10]([CH3:15])([CH3:14])[O:11][C:12]=12
Reactant: CC1(C)Oc2cc3c(cc2S1)SC(C)(C)O3
Reactant: C[Si](C)(C)Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC1(C)Oc2c(cc3c(c2[Si](C)(C)C)OC(C)(C)S3)S1
Reaction time: 0.25 h

Procedure:
The reaction was performed under an argon atmosphere using deoxygenated solvents. 2,2,6,6-tetramethylbenzo[1,2-d:5,4-d']-bis(1,3)oxathiole (6.0 g, 23.6 mmol) was dissolved in dry THF (120 mL). The mixture was cooled on an ice-bath and n-butyllithium (10.8 mL, 2.5M in hexane) was added dropwise over 10 min. After 15 min, chlorotrimethylsilane (6.0 mL, 47.2 mmol) was added dropwise over 5 min. After another 15 min, the reaction mixture was quenched with dietyl ether/aq. NaHCO3, the aqueous layer was extracted with ether and the combined organic layers were washed with water and dried (Na2SO4). After evaporation and chromatography (silica gel, chloroform) essentially pure product (6.3 g, 92%) could be collected.
Reaction SMILES: C([O:8][C@@H:9]1[C@@H:14]([O:15]CC2C=CC=CC=2)[C@H:13]([O:23]CC2C=CC=CC=2)[C@@H:12]([CH2:31][O:32]CC2C=CC=CC=2)[O:11][C@H:10]1[C:40]1[CH:45]=[CH:44][C:43]([Cl:46])=[C:42]([CH2:47][C:48]2[S:49][C:50]([C:53]3[N:58]=[CH:57][CH:56]=[CH:55][N:54]=3)=[CH:51][CH:52]=2)[CH:41]=1)C1C=CC=CC=1.B(F)(F)F.C(=O)([O-])O.[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>C(S)C>[C@@H:10]1([C:40]2[CH:45]=[CH:44][C:43]([Cl:46])=[C:42]([CH2:47][C:48]3[S:49][C:50]([C:53]4[N:54]=[CH:55][CH:56]=[CH:57][N:58]=4)=[CH:51][CH:52]=3)[CH:41]=2)[O:11][C@H:12]([CH2:31][OH:32])[C@@H:13]([OH:23])[C@H:14]([OH:15])[C@H:9]1[OH:8]
Reactant: Clc1ccc([C@@H]2O[C@H](COCc3ccccc3)[C@@H](OCc3ccccc3)[C@H](OCc3ccccc3)[C@H]2OCc2ccccc2)cc1Cc1ccc(-c2ncccn2)s1
Agent: FB(F)F
Agent: O=C([O-])O
Agent: O=S([O-])([O-])=S
Solvent: CCS
Product: OC[C@H]1O[C@@H](c2ccc(Cl)c(Cc3ccc(-c4ncccn4)s3)c2)[C@H](O)[C@@H](O)[C@@H]1O
Temperature: 0 °C
Reaction time: 8 h
Yield: 54.1 %

Procedure:
To a solution of the above 1-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-4-chloro-3-(5(2-pyrimidinyl)-2-thienylmethyl)benzene 55 (90 mg) in ethanethiol (1.5 ml) was added boron trifluoride.ether complex (0.42 ml) at 0° C., and the mixture was stirred at room temperature overnight. The mixture was cooled again to 0° C., and added thereto were a saturated aqueous sodium hydrogen carbonate solution and an aqueous sodium thiosulfate solution. The mixture was extracted with ethyl acetate and tetrahydrofuran, and the extract was dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=19:1-9:1) to give the desired 1-(β-D-glucopyranosyl)-4-chloro-3-(5-(2-pyrimidinyl)-2-thienylmethyl)benzene 56 (27 mg) as pale yellow powder. APCI-Mass m/Z 449/451 (M+H).
Reaction SMILES: C(OC([NH:8][C@H:9]1[C@H:14]([O:15][Si](C(C)(C)C)(C)C)[C@@H:13]([CH3:23])[CH2:12][N:11]([C:24]2[CH:29]=[CH:28][N:27]=[CH:26][C:25]=2[NH:30][C:31]([C:33]2[C:42]([NH:43]C(=O)OCC3C=CC=CC=3)=[CH:41][C:40]3[C:35](=[CH:36][C:37]([N:54]4[CH2:59][CH2:58][N:57]([CH3:60])[CH2:56][CH2:55]4)=[CH:38][CH:39]=3)[N:34]=2)=[O:32])[CH2:10]1)=O)(C)(C)C.[H][H]>CO.[Pd]>[NH2:43][C:42]1[C:33]([C:31]([NH:30][C:25]2[CH:26]=[N:27][CH:28]=[CH:29][C:24]=2[N:11]2[CH2:12][C@H:13]([CH3:23])[C@@H:14]([OH:15])[C@H:9]([NH2:8])[CH2:10]2)=[O:32])=[N:34][C:35]2[C:40]([CH:41]=1)=[CH:39][CH:38]=[C:37]([N:54]1[CH2:59][CH2:58][N:57]([CH3:60])[CH2:56][CH2:55]1)[CH:36]=2
Reactant: C[C@H]1CN(c2ccncc2NC(=O)c2nc3cc(N4CCN(C)CC4)ccc3cc2NC(=O)OCc2ccccc2)C[C@@H](NC(=O)OC(C)(C)C)[C@@H]1O[Si](C)(C)C(C)(C)C
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: C[C@H]1CN(c2ccncc2NC(=O)c2nc3cc(N4CCN(C)CC4)ccc3cc2N)C[C@@H](N)[C@@H]1O

Procedure:
A mixture of benzyl [2-({[4-((3R,4R,5S)-3-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-1-yl)pyridin-3-yl]amino}carbonyl)-7-(4-methylpiperazin-1-yl)quinolin-3-yl]carbamate (0.0055 g, 0.0066 mmol) in 3 mL of MeOH was hydrogenated in the presence of 3 mg of 10% Pd on carbon under a balloon of hydrogen at room temperature for 1 h. The mixture was diluted with 5 mL of MeOH then filtered. The filtrate was concentrated and the resulting residue was treated with 2 mL of MeOH and 2 mL of 4 M HCl in dioxane at room temperature for 1 h. The solution was concentrated under reduced pressure, the residue was dissolved in 4 mL of MeOH and 0.5 mL of NH4OH solution, then filtered through a diatomaceous earth plug. The filtrate was purified by preparative HPLC (XBridge™ C18 column, eluting with a gradient of MeCN/water containing 0.1% NH4OH, at a flow rate of 30 mL/min.) to afford the title compound. LCMS calc. for C26H35N8O2 [M+H]+: m/z=491.3. found: 491.3.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:18][CH2:17][C:12]2([O:16][CH2:15][CH2:14][O:13]2)[C@H:11]([S:19]C(=O)C2C=CC=CC=2)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].NN>ClCCl>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]1[CH2:18][CH2:17][C:12]2([O:13][CH2:14][CH2:15][O:16]2)[C@H:11]([SH:19])[CH2:10]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N[C@@H]1CCC2(OCCO2)[C@H](SC(=O)c2ccccc2)C1
Agent: NN
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N[C@@H]1CCC2(OCCO2)[C@H](S)C1
Reaction time: 24 h
Yield: 95 %

Procedure:
A mixture of thiobenzoic acid S-((6R, 8R)-8-tert-butoxycarbonylamino-1,4-dioxa-spiro[4.5]dec-6-yl)ester+(6S, 8S)diastereomer (695 mg, 1.77 mmol) and hydrazine (80% aq. solution, 0.10 ml, 2.65 mmol) in 7 ml of dichloromethane was stirred for 24 hours. The mixture was diluted with dichloromethane and washed with 1M aqueous HCl, dried and stripped of the solvent to obtain the title compound (490 mg, 95% yield) as yellow-gray oil.
Reaction SMILES: [CH3:1][C:2]1[O:7][C:6](=[O:8])[CH:5]=[C:4]([S:9][C:10]2[CH2:11][S:12](=O)[C@@H:13]3[C@H:33]([NH:34][C:35](=[O:43])[CH2:36][C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[C:32](=[O:44])[N:14]3[C:15]=2[C:16]([O:18][CH:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[CH:3]=1.CC(N(C)C)=O.P(Cl)(Cl)Cl>ClCCl>[CH3:1][C:2]1[O:7][C:6](=[O:8])[CH:5]=[C:4]([S:9][C:10]2[CH2:11][S:12][C@@H:13]3[C@H:33]([NH:34][C:35](=[O:43])[CH2:36][C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=4)[C:32](=[O:44])[N:14]3[C:15]=2[C:16]([O:18][CH:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:17])[CH:3]=1
Reactant: Cc1cc(SC2=C(C(=O)OC(c3ccccc3)c3ccccc3)N3C(=O)[C@@H](NC(=O)Cc4ccccc4)[C@H]3S(=O)C2)cc(=O)o1
Solvent: CC(=O)N(C)C
Solvent: ClP(Cl)Cl
Solvent: ClCCl
Product: Cc1cc(SC2=C(C(=O)OC(c3ccccc3)c3ccccc3)N3C(=O)[C@@H](NC(=O)Cc4ccccc4)[C@H]3SC2)cc(=O)o1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 89.9 %

Procedure:
A stirred solution of diphenylmethyl 3-(6-methyl-2-oxo-2H-pyran-4-ylthio) -7β-phenylacetamidoceph-3-em-4-carboxylate 1-oxide (581 mg) in dichloromethane (5 ml) was cooled in an ice bath and dimethylacetamide (0.25 ml) was added followed by phosphorus trichloride (0.16 ml). The mixture was stirred at 0° C. for 15 mins. and then partitioned between sodium bicarbonate solution and chloroform. The chloroform layer was washed with water, then brine, dried over magnesium sulphate and evaporated. The title compound (509 mg) was isolated by column chromatography of the residue using gradient elution (Kieselgel, 1:1 hexane: ethyl acetate going to neat ethyl acetate). υmax (CHCl3) 3400, 1795, 1725, 1710, and 1680 cm-1. δH (CDCl3) 2.16 (3H, s), 3.33 (1H, d, J 18.1Hz), 3.62 (1H, d, J 17.9Hz), 3.65 (2H, s), 5.03 (1H, d, J 5.1Hz), 5.66 (1H, s) 5.71 (1H, s), 5.94 (1H, dd, J 5.1 and 9.2Hz), 6.96 (1H, s), 6.98 (1H, d, J 9.1Hz), 7.2-7.4 (15H, m). [mass spectrum: +ve ion (3 NOBA, Na+) M Na+ 647].
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:16]([CH2:17][C:18]([OH:20])=O)[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:33][CH2:34][CH2:35][N:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1>O1CCCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:16]([CH2:17][C:18]([NH:33][CH2:34][CH2:35][N:36]3[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]3)=[O:20])[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:6][CH:7]=1
Reactant: NCCN1CCCCC1
Reactant: O=C(O)Cn1c(-c2ccc(Br)cc2)nc2cccnc21
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: O=C(Cn1c(-c2ccc(Br)cc2)nc2cccnc21)NCCN1CCCCC1
Temperature: 25 °C
Reaction time: 3 h
Yield: 72.8 %

Procedure:
A suspension of 2-(4-bromophenyl)-3H-imidazo[4,5-b]pyridine-3-acetic acid (6.0 g, 0.018 mole), 1,1'-carbonyldiimidazole (2.9 g, 0.018 mole) and anhydrous tetrahydrofuran (100 ml) was stirred at room temperature with a stream of nitrogen bubbling through for 3 hours. The nitrogen flow was stopped and a solution of 1-(2-aminoethyl)piperidine (2.3 g, 0.018 mole) in dry tetrahydrofuran (25 ml) was added. The solution was stirred at room temperature under nitrogen for 2 hours. The reaction mixture was concentrated in vacuo and the residue triturated in potassium bicarbonate solution (100 ml) and filtered. The filter cake was washed with water and recrystallized from isopropyl alcohol-isopropyl ether to give 5.8 g (73%) of off-white needles, mp 178°-179° C.
Reaction SMILES: [S:1]([O-:4])([O-:3])=[O:2].[Na+:5].[Na+].[F:7][C:8]([F:12])=[C:9]([F:11])[F:10]>O>[F:7][CH:8]([F:12])[C:9]([F:11])([F:10])[S:1]([O-:4])(=[O:3])=[O:2].[Na+:5]
Reactant: FC(F)=C(F)F
Reactant: O=S([O-])[O-]
Agent: [Na+]
Solvent: O
Product: O=S(=O)([O-])C(F)(F)C(F)F
Temperature: 120 °C
Yield: 24.5 %

Procedure:
The sodium sulphite (151 g) was dissolved in water (500 mL) and taken in a 1000 mL Hastelloy reactor. Tetrafluoroethylene (100 g) was added to the reactor at −130° C. The temperature of the reactor was increased to 120° C. and maintained at 120° C. for 12 hours. The reactor was cooled to 25° C. and unreacted tetrafluoroethylene was vented off. The water of the reaction was removed from reaction mixture by azeotropic distillation to obtain a reaction mass. The reaction mass was extracted with hot ethanol using soxhlet apparatus. The ethanolic solution was concentrated to obtain pure sodium tetrafluoroethane sulfonate (50 g).
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C@@:13]([CH:23]=[CH:24][CH2:25][CH2:26][CH3:27])([CH2:14][O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:12][C@@H:11]([N:28]2[CH:36]=[C:34]([CH3:35])[C:32](=[O:33])[NH:31][C:29]2=[O:30])[C:10]1(O)[OH:37])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:39]1[CH:44]=[CH:43][C:42]([O:45][C:46](Cl)=[S:47])=[CH:41][CH:40]=1>CN(C1C=CN=CC=1)C.N1C=CC=CC=1>[CH2:1]([O:8][C@@H:9]1[C@@:13]([CH:23]=[CH:24][CH2:25][CH2:26][CH3:27])([CH2:14][O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:12][C@@H:11]([N:28]2[CH:36]=[C:34]([CH3:35])[C:32](=[O:33])[NH:31][C:29]2=[O:30])[C@@H:10]1[O:37][C:46]([O:45][C:42]1[CH:43]=[CH:44][CH:39]=[CH:40][CH:41]=1)=[S:47])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: S=C(Cl)Oc1ccccc1
Reactant: CCCC=C[C@]1(COCc2ccccc2)O[C@@H](n2cc(C)c(=O)[nH]c2=O)C(O)(O)[C@@H]1OCc1ccccc1
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Product: CCCC=C[C@]1(COCc2ccccc2)O[C@@H](n2cc(C)c(=O)[nH]c2=O)[C@H](OC(=S)Oc2ccccc2)[C@@H]1OCc1ccccc1
Reaction time: 8 h

Procedure:
The nucleoside 20 (2.8 g, 5.7 mmol) was evaporated thrice with dry pyridine and dissolved in the same. To this pre-cooled solution was added DMAP (0.69 g, 5.7 mmol) and then dropwise was added phenyl chlorothionoformate (1.15 mL, 8.55 mmol) and reaction stirred overnight. Reaction was quenched with saturated solution of NaHCO3 and extracted with dichloromethane. Organic layer was dried over MgSO4 concentrated and chromatographed over silica gel (10-30% ethyl acetate in cyclohexane, v/v) to give 21 as yellowish foam (2.1 g, 3.42 mmol, 60%). Rf=0.60 (30% ethyl acetate in cyclohexane, v/v). 1H NMR (600 MHz, CDCl3) δ: 8.32 (1H, br s, NH), 7.48 (1H, s, H6), 7.48-6.99 (15H, m), 6.4 (1H, d, JH1′,H2′=6.3 Hz, H1′), 5.94 (1H, app t, J=6.0 Hz, H2′), 5.77 (1H, m, H8′), 4.97 (2H, m, H9′ and H9″), 4.77 (1H, d, Jgem=12 Hz, CH2Bn), 4.55 (3H, d, Jgem=12 Hz, CH2Bn), 4.53 (1H, d, JH2′,H3′=5.8 Hz, H3′), 3.74 (1H, d, JH5′,H5″=9.9 Hz, H5″), 3.47 (1H, d, JH5′,H5″=9.9 Hz, H5′), 2.22 (1H, m, H7′), 2.06 (1H, m, H7″), 1.94 (1H, m, H6′), 1.66 (1H, m, H6″), 1.53 (3H, thymine CH3); 13C NMR (125.7 MHz, CDCl3) δ: 194.4 (C═S), 163.3 (C4), 153.3, 150.2 (C2), 138.1 (C8′), 137.3, 137.0, 135.6 (C6), 129.5-121.9 (aromatic), 114.8 (C9′), 111.5 (C5), 87.6 (C4′), 85.1 (C1′), 82.9 (C2′), 78.1 (C3′), 74.9 (CH2Bn), 73.7 (C5′), 73.6 (CH2Bn), 31.6 (C6′), 27.6 (C7′), 12.0 (CH3 thymine); MALDI-TOF m/z [M+H]+ found 629.09, calcd 629.73.
Reaction SMILES: [H-].[Na+].[CH2:3]([C:5]1[CH:9]=[C:8]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[OH:18])[O:7][N:6]=1)[CH3:4].[CH2:19]([CH:21]1[O:23][CH2:22]1)Br.[Cl-].[Na+]>>[CH2:3]([C:5]1[CH:9]=[C:8]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[O:18][CH2:19][CH:21]2[O:23][CH2:22]2)[O:7][N:6]=1)[CH3:4]
Reactant: CCc1cc(C=Cc2ccccc2O)on1
Reactant: BrCC1CO1
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Product: CCc1cc(C=Cc2ccccc2OCC2CO2)on1

Procedure:
This compound is prepared by the method described for Example V, from 5.1 g of 55% strength sodium hydride (0.116 mole), 25.0 g (0.116 mole) of 3-ethyl-5-(2-hydroxystyryl)-isoxazole and 15.9 g (0.116 mole) of epibromohydrin. The reaction mixture is poured into sodium chloride solution and extracted by shaking with diethyl ether. The ether solution is dried over anhydrous sodium sulfate, and concentrated. 29.2 g (93% of theory) of a colorless oil are obtained.
Reaction SMILES: [CH2:1]([C:8]1[CH:9]=[CH:10][C:11]([C:14]([OH:16])=[O:15])=[N:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH2:18](O)[CH3:19]>>[CH2:1]([C:8]1[CH:9]=[CH:10][C:11]([C:14]([O:16][CH2:18][CH3:19])=[O:15])=[N:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCO
Reactant: O=C(O)c1ccc(Cc2ccccc2)cn1
Agent: Cl
Product: CCOC(=O)c1ccc(Cc2ccccc2)cn1

Procedure:
2.0 Grams of 5-benzylpicolinic acid were suspended in 25 ml. of ethanol. The resulting suspension was saturated with hydrogen chloride gas under ice-cooling. After reflux for three hours, the reaction solution was concentrated under reduced pressure. Ether was added thereto to form crystals. The crystals were then recrystallized from a solvent comprising a mixture of acetone/ether to obtain 1.7 g of ethyl 5-benzylpicolinate of a melting point of 109°~111° C.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:38]=[CH:37][C:9]2[N:10]([CH:31]3[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]3)[C:11]([C:13]3[CH:14]=[C:15]4[C:20](=[CH:21][CH:22]=3)[N:19]=[C:18]([C:23](=[O:30])[NH:24][CH:25]([C:27](=O)N)[CH3:26])[CH:17]=[CH:16]4)=[N:12][C:8]=2[CH:7]=1)=[O:5])[CH3:2].[Cl:39][C:40]1[CH:46]=CC(N)=C[CH:41]=1>>[CH2:1]([O:3][C:4]([C:6]1[CH:38]=[CH:37][C:9]2[N:10]([CH:31]3[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]3)[C:11]([C:13]3[CH:14]=[C:15]4[C:20](=[CH:21][CH:22]=3)[N:19]=[C:18]([C:23](=[O:30])[NH:24][C:25]3[CH:27]=[CH:46][C:40]([Cl:39])=[CH:41][CH:26]=3)[CH:17]=[CH:16]4)=[N:12][C:8]=2[CH:7]=1)=[O:5])[CH3:2]
Reactant: Nc1ccc(Cl)cc1
Reactant: CCOC(=O)c1ccc2c(c1)nc(-c1ccc3nc(C(=O)NC(C)C(N)=O)ccc3c1)n2C1CCCCC1
Product: CCOC(=O)c1ccc2c(c1)nc(-c1ccc3nc(C(=O)Nc4ccc(Cl)cc4)ccc3c1)n2C1CCCCC1

Procedure:
The title compound was prepared as described for Compound 497a using 4-chloroaniline in place of L-alaninamide yielding 91 mg yellow solid. MS: 553.23 (M+H+).
Reaction SMILES: [Br:1][C:2]1[C:7]2=[CH:8][N:9]([C:11]3[C:16](Cl)=[CH:15][C:14]([N+:18]([O-:20])=[O:19])=[CH:13][C:12]=3[Cl:21])[N:10]=[C:6]2[C:5]([F:22])=[CH:4][N:3]=1.ClC1C(N2C=C3C(Cl)=NC=C(F)C3=N2)=C(C=C([N+]([O-])=O)C=1)[C:27]#[N:28]>>[Br:1][C:2]1[C:7]2=[CH:8][N:9]([C:11]3[C:12]([Cl:21])=[CH:13][C:14]([N+:18]([O-:20])=[O:19])=[CH:15][C:16]=3[C:27]#[N:28])[N:10]=[C:6]2[C:5]([F:22])=[CH:4][N:3]=1
Reactant: O=[N+]([O-])c1cc(Cl)c(-n2cc3c(Br)ncc(F)c3n2)c(Cl)c1
Reactant: N#Cc1cc([N+](=O)[O-])cc(Cl)c1-n1cc2c(Cl)ncc(F)c2n1
Product: N#Cc1cc([N+](=O)[O-])cc(Cl)c1-n1cc2c(Br)ncc(F)c2n1
Temperature: 100 °C
Yield: 83 %

Procedure:
Following the procedure described for 4-bromo-2-(2,6-dichloro-4-nitrophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine, 3-chloro-2-(4-chloro-7-fluoropyrazolo[4,3-c]pyridin-2-yl)-5-nitrobenzonitrile was heated at 100° C. overnight to afford the title compound as a pale yellow solid (1.38 g, 83% yield). LCMS (Method C): RT=3.62 min, m/z: 396 [M+H+].
Reaction SMILES: [O:1]([C:8]1[CH:13]=[CH:12][C:11]([C:14](=O)[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH2:22][OH:23].C([O-])(=O)C.[Na+]>C(O)C>[OH:23]/[N:22]=[C:14](\[C:11]1[CH:12]=[CH:13][C:8]([O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:9][CH:10]=1)/[C:15]([O:17][CH2:18][CH3:19])=[O:16]
Reactant: CCOC(=O)C(=O)c1ccc(Oc2ccccc2)cc1
Reactant: NO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)/C(=N/O)c1ccc(Oc2ccccc2)cc1
Yield: 27.5 %

Procedure:
A mixture of ethyl 4-phenoxyphenylglyoxylate (37.9 g), hydroxylamine hydrochloride (11.7 g), sodium acetate (17.3 g) and ethanol (200 ml) was heated under reflux for 15 hours. The reaction mixture was concentrated, and the residue was diluted with water and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried (MgSO4), and then concentrated. The residual crystals were recrystallized from toluene-hexane to obtain ethyl E-2-hydroxyimino-2-(4-phenoxyphenyl)acetate (11.0 g, yield 28%) as a colorless oil. m.p. 131-132° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].Br[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>>[CH2:13]([O:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([N+:9]([O-:11])=[O:10])[CH:4]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=[N+]([O-])c1cc(O)ccc1Cl
Reactant: BrCc1ccccc1
Product: O=[N+]([O-])c1cc(OCc2ccccc2)ccc1Cl

Procedure:
A solution of 4-chloro-3-nitro-phenol was reacted with Bromomethyl-benzene using the conditions described in Example 237C to provide 4-benzyloxy-1-chloro-2-nitro-benzene which was treated sequentially using the procedures from Examples 237D and 237E to provide 4-(2-amino-4-benzyloxy-phenylsulfanyl)-phenol.
Reaction SMILES: [P:1]([O-:21])([O-:20])([O:3][CH2:4][CH:5]([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])=[O:2].[CH2:22]([CH:24]1[O:26][CH2:25]1)[Cl:23].[OH-].[Na+:28]>>[P:1]([O-:20])([O:21][CH2:25][CH:24]([OH:26])[CH2:22][Cl:23])([O:3][CH2:4][CH:5]([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])=[O:2].[Na+:28]
Reactant: CCCCCCCCC(CCCCCC)COP(=O)([O-])[O-]
Reactant: ClCC1CO1
Agent: [Na+]
Agent: [OH-]
Product: CCCCCCCCC(CCCCCC)COP(=O)([O-])OCC(O)CCl
Reaction time: 8 h
Yield: 82.3 %

Procedure:
20 g (0.057 moles) of mono2-hexyldecyl phosphate having a purity of 92% (AV1=167.2, AV2=329.8) was dispersed in 59.6 ml of 1N sodium hydroxide aqueous solution, at which the acid value of the reaction system was 39.5. While keeping the reaction system at 80° C., 16.5 g (0.178 moles) of epichlorohydrin was gradually added, followed by agitation at the temperature for 8 hours. The acid value of the reaction system was approximately zero, revealing that the conversion rate of the phosphoric monoester was almost 100%. The reaction solution was analyzed by HPLC. The chromatography showed peaks corresponding to hydrolysate or epichlorhidrine and a new reaction product. The resulting product was collected by HPLC and the solvent was distilled off under reduced pressure to obtain 20.5 g (yield 82.3%) of sodium 2-hexyldecyl 2-hydroxy-3-chloropropyl phosphate.
Reaction SMILES: S([C:5]1[N:6]=[C:7]2[N:11]([C:12]=1C(OCC)=O)[CH:10]=[CH:9][S:8]2)(C)(=O)=O.[CH:18]([SH:21])([CH3:20])[CH3:19]>>[CH:18]([S:21][C:5]1[N:6]=[C:7]2[N:11]([CH:12]=1)[CH:10]=[CH:9][S:8]2)([CH3:20])[CH3:19]
Reactant: CC(C)S
Reactant: CCOC(=O)c1c(S(C)(=O)=O)nc2sccn12
Product: CC(C)Sc1cn2ccsc2n1

Procedure:
In a manner similar to the procedure in Reference Example 1, the oily title compound was prepared from ethyl 6-mesylimidazo[2,1-b]thiazole-5-carboxlate and isopropyl mercaptan. ##STR10##
Reaction SMILES: [Cl:1][C:2]1[CH:22]=[CH:21][C:5]2[CH:6]([N:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[C:7]3[C:12]([CH2:13][S:14][C:4]=2[CH:3]=1)=[CH:11][CH:10]=[CH:9][N:8]=3.[N:23]1[CH:28]=[CH:27][C:26]([S:29][CH2:30][C:31](O)=[O:32])=[CH:25][CH:24]=1>>[Cl:1][C:2]1[CH:22]=[CH:21][C:5]2[CH:6]([N:15]3[CH2:16][CH2:17][N:18]([C:31](=[O:32])[CH2:30][S:29][C:26]4[CH:27]=[CH:28][N:23]=[CH:24][CH:25]=4)[CH2:19][CH2:20]3)[C:7]3[C:12]([CH2:13][S:14][C:4]=2[CH:3]=1)=[CH:11][CH:10]=[CH:9][N:8]=3
Reactant: O=C(O)CSc1ccncc1
Reactant: Clc1ccc2c(c1)SCc1cccnc1C2N1CCNCC1
Product: O=C(CSc1ccncc1)N1CCN(C2c3ccc(Cl)cc3SCc3cccnc32)CC1
Yield: 93.8 %

Procedure:
The title compound (548 mg, 94%) [MS (FAB, M+H)=483.1] was prepared similarly from 1-(8-chloro-5,11-dihydro-[1]benzothiepino[4,3-b]pyridin-11-yl)-piperazine (400 mg, 1.21 mmol) and (4-pyridinylthio)acetic acid (410 mg, 2.42 mmol).