Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([NH:8][CH2:9][CH:10]([CH2:21][OH:22])[CH:11]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[C:15]([Cl:20])[CH:14]=1)[OH:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23]([Si:27](Cl)([CH3:29])[CH3:28])([CH3:26])([CH3:25])[CH3:24].C(N(CC)CC)C>C1COCC1.CN(C)C1C=CN=CC=1>[CH2:1]([NH:8][CH2:9][CH:10]([CH2:21][O:22][Si:27]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:29])[CH3:28])[CH:11]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[C:15]([Cl:20])[CH:14]=1)[OH:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OCC(CNCc1ccccc1)C(O)c1ccc(F)c(Cl)c1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)OCC(CNCc1ccccc1)C(O)c1ccc(F)c(Cl)c1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of (1RS,2SR)-2-[(benzylamino)methyl]-1-(3-chloro-4-fluorophenyl)propane-1,3-diol (the above-mentioned crude product) in THF (170 ml) were added tert-butylchlorodimethylsilane (5.38 g), triethylamine (7.1 ml) and 4-(dimethylamino)pyridine (415 mg) under ice-cooling, and the mixture was stirred at room temperature for 18 hr. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with ethyl acetate. The diluted solution was washed with distilled water, saturated aqueous sodium hydrogen carbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the title compound (14.1 g).
Reaction SMILES: [N:1]1([C:7]2[N:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]3[CH:15]=[C:16]([CH2:20][S:21]([NH2:24])(=[O:23])=[O:22])[CH:17]=[CH:18][CH:19]=3)[N:8]=2)[CH2:6][CH2:5]CC[CH2:2]1.[N:25]1[CH:26]=CN2CC[NH:31][CH2:30][C:29]=12>>[N:31]1[CH:30]=[CH:29][N:25]2[CH2:26][CH2:2][N:1]([C:7]3[N:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]4[CH:15]=[C:16]([CH2:20][S:21]([NH2:24])(=[O:23])=[O:22])[CH:17]=[CH:18][CH:19]=4)[N:8]=3)[CH2:6][C:5]=12
Reactant: c1cn2c(n1)CNCC2
Reactant: NS(=O)(=O)Cc1cccc(Nc2ncnc(N3CCCCC3)n2)c1
Product: NS(=O)(=O)Cc1cccc(Nc2ncnc(N3CCn4ccnc4C3)n2)c1

Procedure:
B46 was prepared following the procedure reported for B1 using Al and 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine. MS (ES) C16H18N8O2S requires: 386. found: 387 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[N:12][C:11]([CH3:14])=[N:10]1)[NH2:5].[C:15](N1C=CC=CC1=O)([N:17]1C=CC=CC1=O)=[S:16].N>ClCCl>[F:1][C:2]1[CH:3]=[C:4]([NH:5][C:15]([NH2:17])=[S:16])[CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[N:12][C:11]([CH3:14])=[N:10]1
Reactant: Cc1ncn(-c2ccc(N)cc2F)n1
Reactant: O=c1ccccn1C(=S)n1ccccc1=O
Agent: N
Solvent: ClCCl
Product: Cc1ncn(-c2ccc(NC(N)=S)cc2F)n1
Temperature: -20 °C
Reaction time: 0.5 h
Yield: 83.9 %

Procedure:
Step S (3): Dichloromethane (125 mL) was added to a flask charged with 3-fluoro-4-(3-methyl-1H-1,2,4-triazol-1-yl)aniline (5.00 g, 26.0 mmol) and 1,1′-thiocarbonyldipyridin-2(1H)-one (6.65 g, 28.6 mmol). The crude reaction was concentrated in vacuo. Methanolic ammonia (2.0 M, 150 mL, 300 mmol) was added at rt to the dark-red solid residue. A light brown precipitate resulted. After stirring for 30 min, the crude reaction mixture was chilled in a −20° C. freezer for 1 h. The solid precipitate was collected using vacuum filtration. The solid was rinsed with cold methanol and dried under high vacuum to afford 1-(3-fluoro-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)thiourea (5.48 g, 84% yield) as an off-white solid. LC-MS (M+H)+ 252.2. 1H NMR (500 MHz, DMSO-d6) δ ppm 10.02 (br. s., 1 H), 8.80 (d, J=2.1 Hz, 1 H), 7.91 (dd, J=13.4, 2.1 Hz, 1 H), 7.66 (t, J=8.7 Hz, 1 H), 7.33 (dd, J=8.4, 2.0 Hz, 1 H), 2.36 (s, 3 H).
Reaction SMILES: [CH3:1][C@:2]12[CH2:20][CH2:19][C@H:18]3[C@@H:7]([CH2:8][CH2:9][C:10]4[C@:15]3([CH2:16][OH:17])[CH2:14][CH2:13][C@H:12]([OH:21])[CH:11]=4)[C@@H:6]1[CH2:5][CH2:4][C@@H:3]2[OH:22].C[Si:24]([CH2:27]C(N)=O)([CH3:26])[CH3:25]>N1C=CC=CC=1>[CH3:25][Si:24]([CH3:27])([CH3:26])[O:21][C@H:12]1[CH2:13][CH2:14][C@@:15]2([CH2:16][O:17][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:10]([CH2:9][CH2:8][C@@H:7]3[C@@H:18]2[CH2:19][CH2:20][C@@:2]2([CH3:1])[C@H:6]3[CH2:5][CH2:4][C@@H:3]2[O:22][Si:24]([CH3:27])([CH3:26])[CH3:25])=[CH:11]1
Reactant: C[Si](C)(C)CC(N)=O
Reactant: C[C@]12CC[C@H]3[C@@H](CCC4=C[C@@H](O)CC[C@@]43CO)[C@@H]1CC[C@@H]2O
Solvent: c1ccncc1
Product: C[C@]12CC[C@H]3[C@@H](CCC4=C[C@@H](O[Si](C)(C)C)CC[C@@]43CO[Si](C)(C)C)[C@@H]1CC[C@@H]2O[Si](C)(C)C

Procedure:
Androst-4-ene-3β,17β,19-triol is dissolved in dry pyridine and trimethylsilylacetamide added thereto. The reaction is completed at room temperature within a few minutes. The pyridine is removed under reduced pressure and the residue purified from an acetone-hexane solution to yield the desired 3β,17β,19-tri(trimethylsiloxy)androst-4-ene.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:22]=[CH:21][C:6]([O:7][CH2:8][C:9]2[N:10]=[C:11]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[O:12][C:13]=2[CH3:14])=[CH:5][CH:4]=1.[OH:23][N:24]1[C:28](=[O:29])[C:27]2=[CH:30][CH:31]=[CH:32][CH:33]=[C:26]2[C:25]1=[O:34].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH3:14][C:13]1[O:12][C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[N:10][C:9]=1[CH2:8][O:7][C:6]1[CH:21]=[CH:22][C:3]([CH2:2][O:23][N:24]2[C:25](=[O:34])[C:26]3=[CH:33][CH:32]=[CH:31][CH:30]=[C:27]3[C:28]2=[O:29])=[CH:4][CH:5]=1
Reactant: Cc1oc(-c2ccccc2)nc1COc1ccc(CCl)cc1
Reactant: O=C1c2ccccc2C(=O)N1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1oc(-c2ccccc2)nc1COc1ccc(CON2C(=O)c3ccccc3C2=O)cc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 92.8 %

Procedure:
A mixture of 4-(4-chloromethylphenoxymethyl)-5-methyl-2-phenyloxazole (5.00 g), N-hydroxyphthalimide (2.59 g), potassium carbonate (4.40 g) and N,N-dimethylformamide (50 ml) was stirred at room temperature for 20 hours, and water (500 ml) was added. The resultant crystals were filtered, and washed with water to obtain N-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyloxy]phthalimide (6.49 g, yield 93%) as colorless crystals. m.p. 155-156° C.
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[O:3][C:4]1[CH:10]=[CH:9][C:7](N)=[CH:6][CH:5]=1.N([O-])=[O:14].[Na+]>OS(O)(=O)=O>[F:1][C:2]([F:12])([F:11])[O:3][C:4]1[CH:10]=[CH:9][C:7]([OH:14])=[CH:6][CH:5]=1
Reactant: Nc1ccc(OC(F)(F)F)cc1
Reactant: O=N[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Product: Oc1ccc(OC(F)(F)F)cc1
Temperature: 0 °C
Reaction time: 2.5 h
Yield: 70.2 %

Procedure:
p-Trifluoromethoxy aniline (49.60 g) was added rapidly dropwise to vigorously stirred 9N aqueous H2SO4 (500 mL) at 40° C. The mixture was heated to dissolve the solid, then cooled to 0° C. To the fine white suspension, a solution of sodium nitrite (19.46 g in 50 mL of H2O) was added portionwise until an immediate positive KI/starch test result was obtained. This cold solution of diazonium salt was added rapidly dropwise to 9N aqueous H2SO4 (500 mL) at 110° C. Stirring and heating was continued for 2.5 hours. The mixture was cooled to 10° C. and extracted with diethyl ether (3×500 mL). The combined organic layers were dried (MgSO4), filtered and evaporated in vacuo, then flash chromatographed on SiO2 using diethyl ether as eluant to give 35.0 g of the desired phenol as a light brown oil. The oil was distilled (b.p.=75°-80° C. at 20 torr.) to afford a yellow liquid.
Reaction SMILES: [C:1]1([CH:11]=[C:12]([CH2:16][C:17]([OH:19])=[O:18])[C:13]([OH:15])=O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1>C(OC(=O)C)(=O)C>[C:1]1([CH:11]=[C:12]2[CH2:16][C:17](=[O:18])[O:19][C:13]2=[O:15])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: O=C(O)CC(=Cc1cccc2ccccc12)C(=O)O
Solvent: CC(=O)OC(C)=O
Product: O=C1CC(=Cc2cccc3ccccc23)C(=O)O1
Temperature: 60 °C
Yield: 70.2 %

Procedure:
A mixture of 24.5 g of 2-(1-naphthylmethylene)succinic acid and 260 ml of acetic anhydride was heated at 60° C. for an hour, and then the reaction mixture was evaporated under reduced pressure. To the residue was added a mixture of benzene and hexane (1/1, by volume). The precipitated crystals were collected by filtration to obtain 16.0 g of 2-(1-naphthylmethylene)succinic anhydride as orange-yellow crystals.
Reaction SMILES: COC1C=C(OC)C=CC=1C[N:6]1[CH2:11][CH2:10][CH2:9][CH:8]([F:12])[S:7]1(=[O:14])=[O:13].FC(F)(F)C(O)=O>C(Cl)Cl>[F:12][CH:8]1[S:7](=[O:14])(=[O:13])[NH:6][CH2:11][CH2:10][CH2:9]1
Reactant: COc1ccc(CN2CCCC(F)S2(=O)=O)c(OC)c1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=S1(=O)NCCCC1F
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 77.3 %

Procedure:
2-(2,4-Dimethoxybenzyl)-6-fluoro-1,2-thiazinane-1,1-dioxide (0.532 g, 1.8 mmol) in methylene chloride (40 mL) was cooled to 0° C. Trifluoroacetic acid (25 mL) was added and the resultant red solution stirred for 1.5 hrs at 0° C., concentrated under reduced pressure. The crude product was purified by silica gel chromatography (20-70% ethyl acetate/hexanes) to give a clear liquid (0.213 g, 79%). 1H NMR (300 MHz, CDCl3) δ 5.35-5.33 (dd, 0.5H, J=5.0, 2.4 Hz), 5.19-5.17 (t, 0.5H, J=3.6 Hz), 4.76 (br s, 1H), 3.52-3.32 (m, 2H), 2.56-2.40 (m, 2H), 1.91-1.81 (m, 1H), 1.59-1.52 (m, 1H).
Reaction SMILES: [C@@H]1(N2C3N=C(N)NC(=O)C=3N=C2)O[C@H](CO)C[C@H]1O.[C@@H:20]1(N2C3N=C(N)NC(=O)C=3N=C2)[O:27][C@H:24]([CH2:25][OH:26])[C@@H:22]([OH:23])[CH2:21]1.[Cl:39][C:40]1[N:48]=[C:47]2[C:43]([NH:44][CH:45]=[N:46]2)=[C:42]([NH2:49])[N:41]=1>>[CH2:21]1[C@H:20]([N:46]2[C:47]3[N:48]=[C:40]([Cl:39])[N:41]=[C:42]([NH2:49])[C:43]=3[N:44]=[CH:45]2)[O:27][C@H:24]([CH2:25][OH:26])[C@H:22]1[OH:23]
Reactant: Nc1nc(Cl)nc2nc[nH]c12
Reactant: Nc1nc2c(ncn2[C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]1
Agent: Nc1nc2c(ncn2[C@@H]2O[C@H](CO)C[C@H]2O)c(=O)[nH]1
Product: Nc1nc(Cl)nc2c1ncn2[C@H]1C[C@H](O)[C@@H](CO)O1
Yield: 81 %

Procedure:
Stereoselective glycosylation of sodium salts of halopurines and analogues with 2-deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranosyl chloride gave β-nucleoside anomers via predominant Walden inversion,17,18 and ammonolysis/deprotection gave CldAdo.19 Although the sodium salt glycosylation usually gave good anomeric stereoselectivity, minor quantities of a anomers and >10% of N7 regioisomers were usually formed.20,21 This requires separations and results in diminished yields of the desired N9 product. Carson et al.1 had reported an enzymatic transfer of the 2-deoxy sugar from thymidine to 2-chloroadenine (ClAde). Holy and coworkers noted that cells of a strain of Escherichia coli performed glycosyl transfer from 2′-deoxyuridine to 2-chloro-6-[(dimethylaminomethylene)amino]purine to give a derivative of CldAdo.22 Very recently Barai, Mikhailopulo, and coworkers23 described an E. coli-mediated glycosyl transfer synthesis of 2,6-diamino-9-(3-deoxy-β-D-erythro-pentofuranosyl)purine,24 and its enzymatic deamination to 3′-deoxyguanosine.24 They reported glycosyl transfer from 2′-deoxyguanosine to ClAde, and claimed a yield of 81% of CldAdo (based on ClAde).23 However, a 3:1 ratio of dGuo/ClAde was employed, so the yield of CldAdo was <27% based on dGuo.
Reaction SMILES: Cl[CH2:2][C:3]1[N:7]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:6]2[CH:16]=[CH:17][CH:18]=[CH:19][C:5]=2[N:4]=1.[CH3:20][Si:21]([CH3:26])([CH3:25])[C:22]#[C:23][CH3:24]>>[CH2:8]([N:7]1[C:6]2[CH:16]=[CH:17][CH:18]=[CH:19][C:5]=2[N:4]=[C:3]1[CH2:2][CH2:24][C:23]#[C:22][Si:21]([CH3:26])([CH3:25])[CH3:20])[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: ClCc1nc2ccccc2n1CCc1ccccc1
Reactant: CC#C[Si](C)(C)C
Product: C[Si](C)(C)C#CCCc1nc2ccccc2n1CCc1ccccc1
Yield: 102.4 %

Procedure:
The title compound was prepared in accordance with the general method of Example 191(D), from of 2-(chloromethyl)-1-phenethyl-1H-benzo[d]imidazole (500 mg, 1.8 mmol) and trimethyl(prop-1-ynyl)silane (249 mg, 2.22 mmol). 1-phenethyl-2-(4-(trimethylsilyl)but-3-ynyl)-1H-benzo[d]imidazole (639 mg, Yield: 100%) was obtained as a brown oil which was used in the next step without purification.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][N:9]2[CH2:14][CH2:13][CH2:12][C:11]3([NH:19][C:18](=[O:20])[C:17]4[CH:21]=[C:22](/[CH:25]=[CH:26]/[C:27]([NH:29][O:30]C5CCCCO5)=[O:28])[CH:23]=[CH:24][C:16]=4[O:15]3)[CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.C(N1CCCC2(NC(=O)C3C=C(/C=C/C(O)=O)C=CC=3O2)C1)C1C=CC=CC=1>C(Cl)Cl.O1CCOCC1>[C:1]1([CH2:7][CH2:8][N:9]2[CH2:14][CH2:13][CH2:12][C:11]3([NH:19][C:18](=[O:20])[C:17]4[CH:21]=[C:22](/[CH:25]=[CH:26]/[C:27]([NH:29][OH:30])=[O:28])[CH:23]=[CH:24][C:16]=4[O:15]3)[CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(/C=C/c1ccc2c(c1)C(=O)NC1(CCCN(CCc3ccccc3)C1)O2)NOC1CCCCO1
Agent: Cl
Agent: O=C(O)/C=C/c1ccc2c(c1)C(=O)NC1(CCCN(Cc3ccccc3)C1)O2
Solvent: ClCCl
Solvent: C1COCCO1
Product: O=C(/C=C/c1ccc2c(c1)C(=O)NC1(CCCN(CCc3ccccc3)C1)O2)NO
Yield: 73.6 %

Procedure:
(±)-(E)-3-{1′-(2-Phenyl-ethyl)-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,3′-piperidin]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide (150 mg, 0.30 mmol) in DCM (5 ml) was treated with 4 M HCl in dioxane (1 ml) as described in Example 30, STEP C to give (±)-(E)-3-{1′-(2-phenyl-ethyl)-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,3′-piperidin]-6-yl}-N-hydroxy-acrylamide (90 mg) as a pale yellow solid (hydrochloride salt).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][CH:13]([OH:26])[CH2:14][C:15]2[C:16](O)=[C:17]3[C:21](=[CH:22][C:23]=2[Cl:24])[CH2:20][CH2:19][CH2:18]3)(=[O:10])=[O:9])=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([O:11][CH2:12][CH:13]2[O:26][C:16]3[C:17]4[CH2:18][CH2:19][CH2:20][C:21]=4[CH:22]=[C:23]([Cl:24])[C:15]=3[CH2:14]2)(=[O:9])=[O:10])=[CH:6][CH:7]=1
Reactant: Cc1ccc(S(=O)(=O)OCC(O)Cc2c(Cl)cc3c(c2O)CCC3)cc1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: Cc1ccc(S(=O)(=O)OCC2Cc3c(Cl)cc4c(c3O2)CCC4)cc1
Yield: 90 %

Procedure:
Treatment of (±)-3-(6-chloro-4-hydroxy-2,3-dihydro-1H-inden-5-yl)-2-hydroxypropyl 4-methylbenzenesulfonate (4.7 g, 0.012 mol) with triphenylphosphine (4.64 g, 0.018 mol) and diisopropylazodicarboxylate (3.57 g, 0.018 mol) generally according to the procedure described for Intermediate 5 gave 4.09 g (91%) of (±)-(4-chloro-3,6,7,8-tetrahydro-2H-indeno[4,5-b]furan-2-yl)methyl 4-methylbenzenesulfonate as a white solid. mp 95-97° C.; Anal. calcd. for C19H19ClO4S: C, 60.23; H, 5.05. Found: C, 60.12; H, 4.97.
Reaction SMILES: [CH2:1]=[O:2].[Cl-].[Mg+2].[Cl-].C(N(CC)CC)C.[F:13][C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][C:15]=1[OH:21].Cl>C(#N)C>[F:13][C:14]1[C:15]([OH:21])=[C:16]([C:17]([CH3:20])=[CH:18][CH:19]=1)[CH:1]=[O:2]
Reactant: Cc1ccc(F)c(O)c1
Reactant: C=O
Agent: Cl
Agent: [Cl-]
Agent: [Mg+2]
Solvent: CC#N
Solvent: CCN(CC)CC
Product: Cc1ccc(F)c(O)c1C=O
Temperature: 90 °C
Reaction time: 240 h

Procedure:
Paraformaldehyde (3.86 g, 133 mmol), magnesium chloride (6.32 g, 66.5 mmol) and triethylamine (11.6 ml, 83.3 mmol) were added to a solution of 2-fluoro-5-methylphenol (4.19 g, 33.3 mmol) in acetonitrile (100 ml), and the mixture was vigorously stirred at 90° C. for 10 days. The reaction mixture was poured into 1N hydrochloric acid and extracted with ethyl acetate. After the organic layer was successively washed with 1N hydrochloric acid, water and a saturated aqueous NaCl solution, and dried with anhydrous sodium sulfate, it was concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography (eluting solvent: hexane/ethyl acetate=4/1) to obtain crude 3-fluoro-2-hydroxy-6-methylbenzaldehyde. According to a method similar to Example (28-3) and Example (28-4), from the crude compound obtained in the above, tert-butyl 2-[(tert-butoxycarbonyl)oxy]-3-fluoro-6-methylbenzoate was obtained (624 mg, three-step total yield: 6%).
Reaction SMILES: [NH2:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[CH:8]=[CH:9][C:10]3[N:11]([CH:13]=[C:14]([NH:16][C:17]([CH:19]4[CH2:21][CH2:20]4)=[O:18])[N:15]=3)[CH:12]=2)=[C:4]([F:24])[CH:3]=1.[F:25][C:26]1[CH:31]=[CH:30][C:29]([N:32]2[CH:37]=[CH:36][CH:35]=[C:34]([C:38](O)=[O:39])[C:33]2=[O:41])=[CH:28][CH:27]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.C(=O)([O-])O.[Na+]>CN(C)C(=O)C.O>[CH:19]1([C:17]([NH:16][C:14]2[N:15]=[C:10]3[CH:9]=[CH:8][C:7]([O:6][C:5]4[CH:22]=[CH:23][C:2]([NH:1][C:38]([C:34]5[C:33](=[O:41])[N:32]([C:29]6[CH:28]=[CH:27][C:26]([F:25])=[CH:31][CH:30]=6)[CH:37]=[CH:36][CH:35]=5)=[O:39])=[CH:3][C:4]=4[F:24])=[CH:12][N:11]3[CH:13]=2)=[O:18])[CH2:21][CH2:20]1
Reactant: O=C(O)c1cccn(-c2ccc(F)cc2)c1=O
Reactant: Nc1ccc(Oc2ccc3nc(NC(=O)C4CC4)cn3c2)c(F)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: O=C([O-])O
Solvent: CC(=O)N(C)C
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(Nc1ccc(Oc2ccc3nc(NC(=O)C4CC4)cn3c2)c(F)c1)c1cccn(-c2ccc(F)cc2)c1=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 108 %

Procedure:
To a solution of N-[6-(4-amino-2-fluorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide (150 mg, 0.460 mmol) in N,N-dimethylacetamide (3.0 mL) were added 1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (161 mg, 0.689 mmol), HATU (262 mg, 0.689 mmol) and N,N-diisopropylethylamine (120 μL, 0.689 mmol), and the mixture was stirred at room temperature for 2 hr. Water and saturated aqueous sodium hydrogen carbonate were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure, and the residue was washed with ethyl acetate and collected by filtration to give the title compound (269 mg, 81%) as a pale-yellow solid.
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:28][O:29][CH2:30][C:31]([OH:33])=[O:32])[C:8]([NH:10][CH:11]2[C:26](=[O:27])[N:13]3[C:14]([C:23]([OH:25])=[O:24])=[C:15]([CH2:18][O:19][C:20](=[O:22])[CH3:21])[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1.C([O-])(=O)C.[Na+:38]>CO>[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:28][O:29][CH2:30][C:31]([OH:33])=[O:32])[C:8]([NH:10][CH:11]2[C:26](=[O:27])[N:13]3[C:14]([C:23]([O-:25])=[O:24])=[C:15]([CH2:18][O:19][C:20](=[O:22])[CH3:21])[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1.[Na+:38].[Na+:38].[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:28][O:29][CH2:30][C:31]([OH:33])=[O:32])[C:8]([NH:10][CH:11]2[C:26](=[O:27])[N:13]3[C:14]([C:23]([O-:25])=[O:24])=[C:15]([CH2:18][O:19][C:20](=[O:22])[CH3:21])[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1
Reactant: CC(=O)OCC1=C(C(=O)O)N2C(=O)C(NC(=O)C(=NOCC(=O)O)c3csc(N)n3)[C@H]2SC1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CO
Product: CC(=O)OCC1=C(C(=O)[O-])N2C(=O)C(NC(=O)C(=NOCC(=O)O)c3csc(N)n3)[C@H]2SC1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
A solution of 0.224 g of the product of Example 4 in 1 ml of a methanolic solution of M sodium acetate and 2 ml of methanol was stirred and was vacuum filtered. The filter was rinsed with methanol and the filtrate was concentrated under reduced pressure to a volume of 1 ml. 5 ml of ethanol were added thereto to induce crystallization and the mixture was stirred at room temperature for 10 minutes and was vacuum filtered. The product was rinsed with ethanol and with ether and dried to obtain 200 mg of the syn isomer of disodium 7-[2-(2-amino-4-thiazolyl)-2-hydroxycarbonylmethyloxyimino-acetamido]-3-acetoxymethyl-ceph-3-eme-4-carboxylate with an Rf=0.3 (acetone with 10% water).
Reaction SMILES: [F:1][C:2]1([F:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4](O)[C:3]1([CH3:13])[CH3:12].[NH:15]1[CH:19]=[C:18]([C:20]([O:22][CH3:23])=[O:21])[N:17]=[CH:16]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.Cl.O1CCOCC1>C1COCC1>[CH3:23][O:22][C:20]([C:18]1[N:17]([CH:4]2[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[C:2]([F:14])([F:1])[C:3]2([CH3:13])[CH3:12])[CH:16]=[N:15][CH:19]=1)=[O:21]
Reactant: COC(=O)c1c[nH]cn1
Reactant: CC1(C)C(O)c2ccccc2C1(F)F
Agent: CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C
Agent: Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: C1COCCO1
Product: COC(=O)c1cncn1C1c2ccccc2C(F)(F)C1(C)C
Temperature: 0 °C
Reaction time: 6 h

Procedure:
To a solution of 3,3-difluoro-2,2-dimethyl-indan-1-ol (388 mg, 1.96 mmol) in THF (16 mL) is added methyl 4-imidazolecarboxylate (CAS#17325-26-7, 370 mg, 2.94 mmol), and triphenylphosphine (770 mg, 2.94 mmol). The reaction is cooled to 0° C. and di-t-butyl azodicarboxylate (670 mg, 2.94 mmol) is added. The reaction is placed at room temperature and permitted to stir for six hours and then is heated to 40° C. overnight. The next day the reaction mixture is cooled to 0° C. and quenched with 4 N HCl in dioxane (5 mL, 20 mmol) and stirred for 30 minutes. The reaction is concentrated to near dryness and diluted with ethyl acetate. The organic layer is extracted three times with 1 N aqueous HCl. The aqueous extracts are combined, neutralized with Na2CO3, and extracted three times with ethyl acetate. The combined organic layers are dried with Na2SO4 filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 1:5) to furnish 3-(3,3-difluoro-2,2-dimethyl-indan-1-yl)-3H-imidazole-4-carboxylic acid methyl ester. MS: (ESI) m/z 307.0 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 0.87 (d, J=2.5 Hz, 3 H), 1.33 (d, J=3.0 Hz, 3 H), 3.96 (s, 3 H), 6.43 (d, J=2.8 Hz, 1 H), 7.17 (s, 1 H), 7.30-7.37 (m, 1 H), 7.56-7.64 (m, 2 H), 7.69-7.76 (m, 1 H), 7.85 (s, 1 H)
Reaction SMILES: [C:1]([O-:15])(=[O:14])[CH2:2][CH2:3][NH:4][C:5](=[O:13])[C@@H:6]([C:8]([CH2:11][OH:12])([CH3:10])[CH3:9])[OH:7].[OH-].[Ca+2:17].[OH-]>>[C:1]([O-:15])(=[O:14])[CH2:2][CH2:3][NH:4][C:5](=[O:13])[C@H:6]([C:8]([CH2:11][OH:12])([CH3:10])[CH3:9])[OH:7].[Ca+2:17].[C:1]([O-:15])(=[O:14])[CH2:2][CH2:3][NH:4][C:5](=[O:13])[C@H:6]([C:8]([CH2:11][OH:12])([CH3:10])[CH3:9])[OH:7]
Reactant: CC(C)(CO)[C@@H](O)C(=O)NCCC(=O)[O-]
Agent: [Ca+2]
Agent: [OH-]
Product: CC(C)(CO)[C@H](O)C(=O)NCCC(=O)[O-]

Procedure:
75 ml of Fraction 2 which contains 4.8 g of pantothenate were brought to a pH of 7, with stirring, by adding solid calcium hydroxide. The resultant calcium D-pantothenate solution or suspension was then dried by evaporating off water on a rotary evaporator and 8.98 g of a light-brown calcium D-pantothenate powder were obtained which has a content of 57% calcium D-pantothenate. This powder has no tendency to stick together and has good product properties.
Reaction SMILES: [C:1]1([S:7]Cl)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH:9][C:10]1[CH:15]=[C:14]([CH3:16])[O:13][C:12](=[O:17])[CH:11]=1.Cl>C1C=CC=CC=1>[OH:9][C:10]1[CH:15]=[C:14]([CH3:16])[O:13][C:12](=[O:17])[C:11]=1[S:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: ClSc1ccccc1
Reactant: Cc1cc(O)cc(=O)o1
Agent: Cl
Solvent: c1ccccc1
Product: Cc1cc(O)c(Sc2ccccc2)c(=O)o1
Yield: 99 %

Procedure:
Benzenesulfenyl chloride (7.2 g., 0.050 mol) dissolved in benzene (15 ml.) was added to a rapidly stirred slurry of 4-hydroxy-6-methyl-2-pyrone (6.3 g., 0.050 mol) in benzene (135 ml.). There was no apparent reaction at ambient temperature, but upon heating hydrogen chloride was evolved. After heating at reflux for 2 hours, the mixture was cooled and filtered to give 11.6 g. colorless crystals, m. 160°-162.5°C., 99 percent yield.
Reaction SMILES: [Cl:1][C:2]1[C:3]([F:11])=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[N+:12]([O-])([OH:14])=[O:13]>>[Cl:1][C:2]1[C:3]([F:11])=[C:4]2[C:10]([N+:12]([O-:14])=[O:13])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1
Reactant: O=[N+]([O-])O
Reactant: Fc1c(Cl)cnc2[nH]ccc12
Product: O=[N+]([O-])c1c[nH]c2ncc(Cl)c(F)c12
Reaction time: 0.17 h
Yield: 86 %

Procedure:
5-Chloro-4-fluoro-1H-pyrrolo[2,3-b]pyridine (1.2 g, 7.0 mmol) was added slowly to fuming nitric acid (10 mL) at 0° C. Upon completion of the addition, the reaction was stirred for 10 minutes, and then quenched with ice. Water was added until a precipitate formed, which was filtered, washed with water and dried to give the product 5-chloro-4-fluoro-3-nitro-1H-pyrrolo[2,3-b]pyridine (1.3 g, 86% yield).