Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1](Cl)[CH2:2][CH2:3][CH2:4][C:5]#[C:6]/[CH:7]=[CH:8]\[CH2:9][CH3:10].[C:12]([O-:15])(=[O:14])[CH3:13].[Na+].CN(C)C(=O)C>[I-].[Na+].O>[C:12]([O:15][CH2:1][CH2:2][CH2:3][CH2:4][C:5]#[C:6]/[CH:7]=[CH:8]\[CH2:9][CH3:10])(=[O:14])[CH3:13]
Reactant: CC/C=C\C#CCCCCCl
Reactant: CC(=O)[O-]
Agent: [I-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)N(C)C
Product: CC/C=C\C#CCCCCOC(C)=O
Temperature: 122.5 °C
Reaction time: 6 h
Yield: 93 %

Procedure:
In a reactor equipped with a stirrer, a cooling condenser, a dropping funnel and a thermometer were placed Z-7-decen-5-yn-yl chloride (170.7 g: 1.0 mol), sodium acetate (98.4 g: 1.2 mol), sodium iodide (8.9 g: 0.06 mol) and N,N-dimethylacetamide (113.2 g), and stirred at from 120 to 125° C. for 6 hours. After the completion of the reaction was confirmed by gas chromatography, water (350.0 g) was added to the reaction mixture. The organic phase separated from the aqueous phase was washed with an aqueous 1.0% by weight sodium bicarbonate solution (250.0 g). The organic phase was subjected to removal of solvent under reduced pressure, followed by dehydration. The residue was then distilled under reduced pressure to obtain Z-7-decen-5-yn-yl acetate [bp: from 75 to 79° C./0.13 KPa, 181.4 g, 0.93 mol]. [Yield: 93.4%]
Reaction SMILES: CN(C)/[CH:3]=[CH:4]/[C:5]([C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=1)=O.[NH2:15][C:16]([NH2:18])=[S:17].C(=O)([O-])[O-].[K+].[K+]>C(O)C>[Cl:13][C:10]1[CH:11]=[CH:12][C:7]([C:5]2[CH:4]=[CH:3][N:18]=[C:16]([SH:17])[N:15]=2)=[CH:8][CH:9]=1
Reactant: CN(C)/C=C/C(=O)c1ccc(Cl)cc1
Reactant: NC(N)=S
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: Sc1nccc(-c2ccc(Cl)cc2)n1
Temperature: 85 °C

Procedure:
To a solution of (2E)-3-(dimethylamino)-1-(4-chlorophenyl)prop-2-en-1-one (1.5 g, 7.2 mmol) in ethanol (25 ml) was added thiourea (0.60 g, 7.9 mmol) and potassium carbonate (K2CO3) (1.19 g. 8.63 mmol). The resulting suspension was heated to 85° C. for 12 hours then cooled to ambient temperature. The resulting solid was collected and thoroughly washed with water and hexanes to provide a beige solid: EI-MS (m/z) 222 [M+1]+.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:23]2[CH:28]=[CH:27][C:26]([NH2:29])=[CH:25][CH:24]=2)([C:16]2[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=2)[C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[N:30]1[C:37](Cl)=[N:36][C:34]([Cl:35])=[N:33][C:31]=1[Cl:32].C([O-])([O-])=O.[Na+].[Na+].O>CC(C)=O>[Cl:35][C:34]1[N:33]=[C:31]([Cl:32])[N:30]=[C:37]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]([C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:37]4[N:36]=[C:34]([Cl:35])[N:33]=[C:31]([Cl:32])[N:30]=4)=[CH:18][CH:17]=3)([C:23]3[CH:28]=[CH:27][C:26]([NH:29][C:37]4[N:36]=[C:34]([Cl:35])[N:33]=[C:31]([Cl:32])[N:30]=4)=[CH:25][CH:24]=3)[C:9]3[CH:10]=[CH:11][C:12]([NH:15][C:37]4[N:36]=[C:34]([Cl:35])[N:33]=[C:31]([Cl:32])[N:30]=4)=[CH:13][CH:14]=3)=[CH:6][CH:7]=2)[N:36]=1
Reactant: Clc1nc(Cl)nc(Cl)n1
Reactant: Nc1ccc(C(c2ccc(N)cc2)(c2ccc(N)cc2)c2ccc(N)cc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: O
Product: Clc1nc(Cl)nc(Nc2ccc(C(c3ccc(Nc4nc(Cl)nc(Cl)n4)cc3)(c3ccc(Nc4nc(Cl)nc(Cl)n4)cc3)c3ccc(Nc4nc(Cl)nc(Cl)n4)cc3)cc2)n1
Reaction time: 1 h
Yield: 68.3 %

Procedure:
A solution of tetrakis(4-aminophenyl)methane (4.57 grams, 12.0 mmol; prepared as described in Example C) in acetone (96 milliliters) was added dropwise at 0° C. to a stirred solution of cyanuric chloride (9.06 grams, 49.1 mmol; obtained from Aldrich Chemical Co., Milwaukee, Wis.) in acetone (144 milliliters). The resulting mixture was kept at 0° C. for 1 hour, treated with Na2CO3 (5.21 grams, 49.2 mmol), and poured into water (960 milliliters). The precipitate was separated by filtration, washed with water, and dried to give the tetrakis[4-[(2,4-dichloro-1,3,5-triazin-6-yl)amino]phenyl]methane (7.97 grams, 8.20 mmol, 68 percent yield) as a colorless solid: mp>310° C.; 1H NMR (400 MHz, DMSO-d6, 25° C.) δ 7.18 (d, 8H, 3J=8.7 Hz), 7.55 (d, 8H, 3J=8.7 Hz), 11.18 (s, 4H); 13C NMR (75.4 MHz, DMSO-d6, 25° C.) δ 64.1, 121.7, 131.7, 135.8, 143.8, 164.6, 169.7, 170.7; MS (FAB, 2-nitrobenzyl alcohol) m/e 969. Anal. Calcd for C37H20Cl8N16: C, 45.71; H, 2.07; N, 23.05. Found: C, 46.03; H, 2.09; N, 22.61.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[N:14]=[C:15]3[C:21]([C:22](O)=[O:23])=[CH:20][NH:19][C:16]3=[N:17][CH:18]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].[NH2:25][CH2:26][CH:27]([OH:29])[CH3:28]>CN(C=O)C>[OH:29][CH:27]([CH3:28])[CH2:26][NH:25][C:22]([C:21]1[C:15]2[C:16](=[N:17][CH:18]=[C:13]([C:5]3[CH:6]=[C:7]([O:11][CH3:12])[C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=3)[N:14]=2)[NH:19][CH:20]=1)=[O:23]
Reactant: CC(O)CN
Reactant: COc1cc(-c2cnc3[nH]cc(C(=O)O)c3n2)cc(OC)c1OC
Solvent: CN(C)C=O
Product: COc1cc(-c2cnc3[nH]cc(C(=O)NCC(C)O)c3n2)cc(OC)c1OC

Procedure:
2-(3,4,5-Trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2-hydroxy-propyl)-amide was prepared starting from 2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid and 1-amino-propan-2-ol following the general procedures described in these Examples but with DMF as solvent. MP 201.9-202.6° C., M+H 387.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[CH3:19][Si:20]([C:23]#[CH:24])([CH3:22])[CH3:21].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[I-].Cl>N1CCCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C.O>[CH2:14]([C:11]1[CH:12]=[CH:13][C:8]([C:5]2[CH:6]=[CH:7][C:2]([C:24]#[C:23][Si:20]([CH3:22])([CH3:21])[CH3:19])=[CH:3][CH:4]=2)=[CH:9][CH:10]=1)[CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCc1ccc(-c2ccc(Br)cc2)cc1
Reactant: C#C[Si](C)(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: Cl
Agent: [I-]
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1CCNCC1
Product: CCCCCc1ccc(-c2ccc(C#C[Si](C)(C)C)cc2)cc1
Temperature: 90 °C

Procedure:
A mixture of 4-bromo-4'-pentylbiphenyl (5.04 g), trimethylsilylacetylene (2.4 ml), tetrakis(triphenylphosphine)palladium (0.96 g), triphenylphosphine (0.22 g) and cuproous iodide (95 mg) in piperidine (10 ml) was heated for an hour under atmospheric pressure of nitrogen at 90° C. The reaction mixture was poured into a mixture of cold water and ethyl acetate, and adjusted to about pH 1 with 6N hydrochloric acid. The separated organic layer was washed with water and brine, and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give crude (2-[4-(4-pentylphenyl)phenyl]-1-trimethylsilylacetylene, which was used for the next reaction without further purification. Crude mixture was dissolved in a mixture of dichloromethane (10 ml) and methanol (10 ml), and to the solution was added potassium carbonate (2.75 g) at 0° C. The mixture was allowed to warm to ambient temperature, and stirred for another 2 hours. The reaction mixture was poured into a mixture of cold water and ethyl acetate, and the resultant precipitate was filtered off. The filtrate was adjusted to about pH 7 with 1N hydrochloric acid, and washed with brine, and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was evaporated under reduced pressure to give a crude powder, which was subjected to column chromatography on silica gel (300 ml), and eluted with a mixture of (n-hexane : ethyl acetate=99:1-97:3, V/V) to give 4-(4-Pentylphenyl)phenylacetylene (2.09 g).
Reaction SMILES: [CH2:1]([O:3][C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:6]([C:22](O)=[O:23])[C:5]=1[C:25](O)=[O:26])[CH3:2].[NH2:28][C:29]1[CH:34]=[CH:33][C:32]([CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:31][C:30]=1[F:41]>CN(C1C=CN=CC=1)C.C(O)(=O)C>[CH2:1]([O:3][C:4]1[C:5]2[C:25](=[O:26])[N:28]([C:29]3[CH:34]=[CH:33][C:32]([CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:31][C:30]=3[F:41])[C:22](=[O:23])[C:6]=2[C:7]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=12)[CH3:2]
Reactant: CCOc1c(C(=O)O)c(C(=O)O)c(OCc2ccccc2)c2ccccc12
Reactant: CCOC(=O)Cc1ccc(N)c(F)c1
Agent: CN(C)c1ccncc1
Solvent: CC(=O)O
Product: CCOC(=O)Cc1ccc(N2C(=O)c3c(c(OCc4ccccc4)c4ccccc4c3OCC)C2=O)c(F)c1
Yield: 110.2 %

Procedure:
A mixture of 1-(ethyloxy)-4-[(phenylmethyl)oxy]-2,3-naphthalenedicarboxylic acid (1.40 g, 3.32 mmol), ethyl (4-amino-3-fluorophenyl)acetate (1.24 g, 6.30 mmol) and DMAP (0.121 g, 0.995 mmol) were heated to 120° C. in acetic acid (20 ml) for 6 hours. The reaction mixture was triturated with water and the resulting yellow solid was collected by filtration and dried in the vacuum oven to give the title compound (1.93 g, 3.66 mmol). LC/MS: Rt=3.95, [MH]+ 528.
Reaction SMILES: O[C:2]1([C:16]2[C:24]([OH:25])=[CH:23][C:19]3[O:20][CH2:21][O:22][C:18]=3[CH:17]=2)[C:10]2[C:5](=[C:6]([C:11]([F:14])([F:13])[F:12])[CH:7]=[CH:8][CH:9]=2)[NH:4][C:3]1=[O:15].FC(F)(F)C(O)=O.C([SiH](CC)CC)C>>[OH:25][C:24]1[C:16]([CH:2]2[C:10]3[C:5](=[C:6]([C:11]([F:14])([F:13])[F:12])[CH:7]=[CH:8][CH:9]=3)[NH:4][C:3]2=[O:15])=[CH:17][C:18]2[O:22][CH2:21][O:20][C:19]=2[CH:23]=1
Reactant: O=C1Nc2c(C(F)(F)F)cccc2C1(O)c1cc2c(cc1O)OCO2
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Product: O=C1Nc2c(cccc2C(F)(F)F)C1c1cc2c(cc1O)OCO2
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 88.1 %

Procedure:
To a solution of 3-hydroxy-3-(6-hydroxy-1,3-benzodioxol-5-yl)-7-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one (7.06 g, 20.0 mmol) in anhydrous trifluoroacetic acid (21.0 mL, 9.12 g, 80 mmol) was added triethylsilane (12.8 mL, 9.30 g, 80.0 mmol) at ambient temperature. The reaction mixture was stirred at ambient temperature for 0.5 h. The reaction mixture was quenched with water (50.0 mL). The mixture was extracted with ethyl acetate (2×150 mL). The organic solution was washed with saturated ammonium chloride (3×75 mL), dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was triturated with diethyl ether to afford 3-(6-hydroxy-1,3-benzodioxol-5-yl)-7-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one (5.94 g, 88%) as colourless solid: 1H NMR (300 MHz, DMSO-d6) δ 10.81 (s, 1H), 9.25 (br, 1H), 7.37 (d, J=8.0 Hz, 1H), 7.12 (d, J=7.3 Hz, 1H), 6.98 (dd, J=7.7, 7.7 Hz, 1H), 6.71 (s, 1H), 5.88 (s, 2H), 4.65 (s, 1H); 13C NMR (75 MHz, DMSO-d6) δ 178.7, 150.5, 147.4, 140.5, 140.1, 133.3, 127.8, 124.3, 124.2, 121.6, 115.5, 110.8, 110.3, 101.3, 98.2, 48.1; MS (ES+) m/z 338.3 (M+1).
Reaction SMILES: [Si](OCC1C=CC(NC(=O)C=C)=C(Cl)C=1)(C(C)(C)C)(C)C.OC(C1SC=CC=1)(C1SC=CC=1)C(O[C@H]1CC[C@H](NC)CC1)=O.[OH:45][C:46]([C:86]1[S:87][CH:88]=[CH:89][CH:90]=1)([C:81]1[S:82][CH:83]=[CH:84][CH:85]=1)[C:47]([O:49][C@H:50]1[CH2:55][CH2:54][C@H:53]([N:56]([CH2:58][CH2:59][C:60]([NH:62][C:63]2[CH:68]=[C:67](OC)[C:66]([CH2:71][O:72][Si:73]([C:76]([CH3:79])([CH3:78])[CH3:77])([CH3:75])[CH3:74])=[CH:65][C:64]=2[Cl:80])=[O:61])[CH3:57])[CH2:52][CH2:51]1)=[O:48]>ClCCl>[OH:45][C:46]([C:81]1[S:82][CH:83]=[CH:84][CH:85]=1)([C:86]1[S:87][CH:88]=[CH:89][CH:90]=1)[C:47]([O:49][C@H:50]1[CH2:51][CH2:52][C@H:53]([N:56]([CH2:58][CH2:59][C:60]([NH:62][C:63]2[CH:68]=[CH:67][C:66]([CH2:71][O:72][Si:73]([C:76]([CH3:79])([CH3:78])[CH3:77])([CH3:75])[CH3:74])=[CH:65][C:64]=2[Cl:80])=[O:61])[CH3:57])[CH2:54][CH2:55]1)=[O:48]
Reactant: COc1cc(NC(=O)CCN(C)[C@H]2CC[C@H](OC(=O)C(O)(c3cccs3)c3cccs3)CC2)c(Cl)cc1CO[Si](C)(C)C(C)(C)C
Agent: C=CC(=O)Nc1ccc(CO[Si](C)(C)C(C)(C)C)cc1Cl
Agent: CN[C@H]1CC[C@H](OC(=O)C(O)(c2cccs2)c2cccs2)CC1
Solvent: ClCCl
Product: CN(CCC(=O)Nc1ccc(CO[Si](C)(C)C(C)(C)C)cc1Cl)[C@H]1CC[C@H](OC(=O)C(O)(c2cccs2)c2cccs2)CC1

Procedure:
Obtained as a beige solid (45%) starting from N-[4-({[tert-butyl(dimethyl)silyl]oxy}-methyl)-2-chlorophenyl]-acrylamide (intermediate 47; 0.56 g, 1.73 mmol) and trans-4-(methylamino)cyclohexyl hydroxy(di-2-thienyl)acetate (intermediate 5; 0.5 g, 1.42 mmol) in 14 ml dichloromethane and following the experimental procedure as described for intermediate 41.
Reaction SMILES: [CH:1]1([C:11]([OH:13])=O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[CH:14]([C:17]1[CH:22]=[CH:21][C:20]([NH:23][CH2:24][C:25]2[CH:26]=[N:27][N:28]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH:29]=2)=[CH:19][CH:18]=1)([CH3:16])[CH3:15]>>[CH:14]([C:17]1[CH:18]=[CH:19][C:20]([N:23]([CH2:24][C:25]2[CH:26]=[N:27][N:28]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH:29]=2)[C:11]([CH:1]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH2:4][CH2:3][CH2:2]2)=[O:13])=[CH:21][CH:22]=1)([CH3:16])[CH3:15]
Reactant: CC(C)c1ccc(NCc2cnn(-c3ccccc3)c2)cc1
Reactant: O=C(O)C1CCCc2ccccc21
Product: CC(C)c1ccc(N(Cc2cnn(-c3ccccc3)c2)C(=O)C2CCCc3ccccc32)cc1
Yield: 47 %

Procedure:
By the reaction and treatment in the same manner as in Example 12 using 1,2,3,4-tetrahydronaphthalene-1-carboxylic acid (0.35 g) and (4-isopropylphenyl)[(1-phenylpyrazol-4-yl)methyl]amine (0.58 g) as starting materials, N-(4-isopropylphenyl)-N-[(1-phenylpyrazol-4-yl)methyl]-1,2,3,4-tetrahydronaphthalene-1-carboxamide (0.42 g) was obtained.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.C[O-].[Na+].[I-].[K+].Br[CH:15]([C:20]1[CH:25]=[CH:24][C:23]([O:26][C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=2)=[CH:22][CH:21]=1)[C:16]([O:18]C)=[O:17].[OH-].[K+].Cl>CO.C1C=CC=CC=1.O.C(=O)(O)[O-].[Na+].C(O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH:15]([C:20]2[CH:21]=[CH:22][C:23]([O:26][C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=3)=[CH:24][CH:25]=2)[C:16]([OH:18])=[O:17])=[CH:4][CH:3]=1
Reactant: Oc1ccc(F)cc1
Reactant: COC(=O)C(Br)c1ccc(Oc2ccc(Cl)cc2)cc1
Agent: C[O-]
Agent: Cl
Agent: O=C([O-])O
Solvent: O
Solvent: c1ccccc1
Solvent: CO
Product: O=C(O)C(Oc1ccc(F)cc1)c1ccc(Oc2ccc(Cl)cc2)cc1

Procedure:
To a solution of 2.80 g of p-fluorophenol and 1.19 g of sodium methoxide in 40 ml of methanol is added 50 mg of potassium iodide and 7.11 g of methyl α-bromo-α-[p-(p-chlorophenoxy)phenyl]acetate in 10 ml of benzene. The mixture is refluxed for 20 hours and the solvent removed under vacuum. To the residue is added water and the mixture is extracted with ether. The ether extracts are washed with 10% potassium carbonate and with water and dried (MgSO4). The solvent is removed under vacuum to give a tan oil. The oil is dissolved in 60 ml. of ethanol and 6 ml of water and 5 g of potassium hydroxide is added. The mixture is refluxed for 3.5 hours, acidified with concentrated hydrochloric acid, diluted with water and poured onto ice. The mixture is extracted with chloroform and the extracts washed with water and dried over magnesium sulfate. Concentration in vacuo gives an oil. The oil is dissolved in aqueous sodium bicarbonate and the mixture extracted with chloroform. The aqueous layer is acidified with concentrated hydrochloric acid, extracted with ether and the extracts dried (MgSO4). Removal of the solvent in vacuo gives the product as a tan oil. A small sample is crystallized, mp 106°-111° C.
Reaction SMILES: P(Cl)(Cl)(Cl)=O.C[N+](C)=CCl.[Cl-].[O:12]1[C:17]([C:18](=[N:22][O:23][CH2:24][CH:25]=[CH2:26])[C:19]([OH:21])=O)=[CH:16][S:15][CH2:14][CH2:13]1.[NH2:27][CH:28]1[C:38](=[O:39])[N:30]2[C:31]([C:35]([OH:37])=[O:36])=[CH:32][CH2:33][S:34][C@H:29]12.C[Si](CC(N)=O)(C)C.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.O.CN(C)C=O>[O:12]1[C:17]([C:18](=[N:22][O:23][CH2:24][CH:25]=[CH2:26])[C:19]([NH:27][CH:28]2[C:38](=[O:39])[N:30]3[C:31]([C:35]([OH:37])=[O:36])=[CH:32][CH2:33][S:34][C@H:29]23)=[O:21])=[CH:16][S:15][CH2:14][CH2:13]1
Reactant: NC1C(=O)N2C(C(=O)O)=CCS[C@H]12
Reactant: C=CCON=C(C(=O)O)C1=CSCCO1
Agent: C[N+](C)=CCl
Agent: C[Si](C)(C)C(C(N)=O)[Si](C)(C)C
Agent: C[Si](C)(C)CC(N)=O
Solvent: CCOC(C)=O
Solvent: O
Solvent: O=P(Cl)(Cl)Cl
Product: C=CCON=C(C(=O)NC1C(=O)N2C(C(=O)O)=CCS[C@H]12)C1=CSCCO1
Reaction time: 0.33 h
Yield: 81.3 %

Procedure:
N,N-dimethylformamide (0.175 g.), phosphoryl chloride (0.367 g.) and ethyl acetate (0.5 ml.) were treated in a conventional manner to prepare a Vilsmeier reagent and the reagent was added to ethyl acetate (5 ml.). To the solution was added 2-(2,3-dihydro-1,4-oxathiin-6-yl)-2-allyloxyiminoacetic acid (syn isomer, 0.500 g.) at -15° C. and stirred at the same temperature for 20 minutes to give an activated acid solution. The solution was added all at once to a solution of 7-amino-3-cephem-4-carboxylic acid (0.524 g.), trimethylsilylacetamide (1.4 g.) and bis(trimethylsilyl)acetamide (1.5 ml.) in ethyl acetate (7.5 ml.) at -15° C. and stirred at the same temperature for 2 hours. Water (10 ml.) was added to the resultant solution, adjusted to pH 7.0 with an aqueous solution of sodium bicarbonate and the aqueous layer was separated. The aqueous solution was adjusted to pH 3 with 10% hydrochloric acid. The precipitates were collected by filtration and washed with water to give 7-[2-(2,3-dihydro-1,4-oxathiin-6-yl)-2-allyloxyiminoacetamido]-3-cephem-4-carboxylic acid (syn isomer, 0.73 g.).
Reaction SMILES: F[C:2]1[CH:25]=[CH:24][C:5]([CH2:6][N:7]2[C:11](=[O:12])[N:10]([C:13]3[S:17][C:16]([C:18]([O:20]CC)=[O:19])=[C:15]([CH3:23])[CH:14]=3)[CH:9]=[N:8]2)=[CH:4][CH:3]=1.C(N1C(=O)N(C2C(C)=C(C([O-])=O)SC=2)C=N1)C1C=CC=CC=1>>[CH2:6]([N:7]1[C:11](=[O:12])[N:10]([C:13]2[S:17][C:16]([C:18]([OH:20])=[O:19])=[C:15]([CH3:23])[CH:14]=2)[CH:9]=[N:8]1)[C:5]1[CH:24]=[CH:25][CH:2]=[CH:3][CH:4]=1
Reactant: CCOC(=O)c1sc(-n2cnn(Cc3ccc(F)cc3)c2=O)cc1C
Agent: Cc1c(-n2cnn(Cc3ccccc3)c2=O)csc1C(=O)[O-]
Product: Cc1cc(-n2cnn(Cc3ccccc3)c2=O)sc1C(=O)O
Yield: 86 %

Procedure:
Following the procedure as described in Example 30, making variations as required to replace ethyl 5-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-3-methylthiophene-2-carboxylate with ethyl 5-(1-benzyl-5-oxo-1H-1,2,4-triazol-4(5H)-yl-3-methylthiophene-2-carboxylate, the title compound was obtained as a colorless solid in 86% yield: NMR (300 MHz, DMSO-d6) δ 12.99 (br s, 1H), 8.75 (s, 1H), 7.40-7.24 (m, 6H), 4.97 (s, 2H), 2.46 (s, 3H); MS (ES−) m/z 314.2 (M−1).
Reaction SMILES: C([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:23])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:11][C:10]=1[O:24][CH3:25])C1C=CC=CC=1>ClCCl.Br.C(O)(=O)C>[OH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:23])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:11][C:10]=1[O:24][CH3:25]
Reactant: COc1cc(C(=O)Cc2ccccc2)ccc1OCc1ccccc1
Agent: Br
Solvent: CC(=O)O
Solvent: ClCCl
Product: COc1cc(C(=O)Cc2ccccc2)ccc1O
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
A solution of 5.9 g, (17.8 mmol) of the above ketone in a mixture of dichloromethane (60 mL) and 30% hydrobromic acid in acetic acid (27 mL) was stirred for 1.5 h at room temperature and then the dichloromethane was evaporated at reduced pressure and the reaction mixture was poured onto 200 mL of an ice/water mixture. The precipitate formed was filtered off, and dried under vacuum to provide 1-(4-hydroxy-3-methoxyphenyl)-2-phenyl-1-ethanone as beige crystals, m.p. 107 to 108° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([C:13]([OH:15])=O)[S:11][CH:12]=2)=[CH:4][CH:3]=1.[NH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1.C(Cl)CCl.C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]([C:13]([N:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)=[O:15])[S:11][CH:12]=2)=[CH:6][CH:7]=1
Reactant: C1CCNCC1
Reactant: O=C(O)c1nc(-c2ccc(Cl)cc2)cs1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: O=C(c1nc(-c2ccc(Cl)cc2)cs1)N1CCCCC1
Temperature: 0 °C
Reaction time: 15 h
Yield: 32.4 %

Procedure:
To a solution of 4-(4-chlorophenyl)thiazole-2-carboxylic acid (prepared according to the procedure given in US 2007/32531, 1.00 g, 4.17 mmol) in DMF (10 ml) was added HOST (0.96 g, 6.26 mmol) at room temperature, followed by the addition of piperidine (0.42 g, 5.01 mmol). The reaction mixture was cooled to 0° C. and to this were added EDC (1.20 g, 6.26 mmol) and triethylamine (2.11 g, 2.91 ml, 20.86 mmol). The reaction mixture was stirred at room temperature for 15 hr and the progress of reaction was monitored by TLC. The reaction mixture was concentrated under reduced pressure. The residue so obtained was taken in ethyl acetate (50 ml) and washed with saturated sodium bicarbonate solution (1×40 ml), brine (1×20 ml) and organic layers separated were dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to get a crude product. The crude product was purified by column chromatography over silica gel (100-200 mesh) using 40% ethyl acetate in hexanes as an eluent to obtain the title compound (0.41 g, 32.4%). MS: m/z 308 (M+1).
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([CH:16]3[N:20]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[Cl:27])[N:19]=[C:18]([C:28]([F:34])([F:33])[C:29]([F:32])([F:31])[F:30])[CH2:17]3)[CH:11]=2)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[BH4-].[Na+]>CO>[Cl:27][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[N:20]1[CH:16]([C:12]2[CH:11]=[C:10]([C:7]3[CH:8]=[CH:9][C:4]([CH:1]([OH:3])[CH3:2])=[CH:5][CH:6]=3)[CH:15]=[CH:14][CH:13]=2)[CH2:17][C:18]([C:28]([F:34])([F:33])[C:29]([F:30])([F:31])[F:32])=[N:19]1
Reactant: CC(=O)c1ccc(-c2cccc(C3CC(C(F)(F)C(F)(F)F)=NN3c3ccccc3Cl)c2)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CC(O)c1ccc(-c2cccc(C3CC(C(F)(F)C(F)(F)F)=NN3c3ccccc3Cl)c2)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 85.9 %

Procedure:
5-(4′-Acetyl-biphenyl-3-yl)-1-(2-chloro-phenyl)-3-pentafluoroethyl-4,5-dihydro-1H-pyrazole (18.0 mg, 0.04 mmol) prepared in Example 107 and sodium borohydride (2.0 mg, 0.06 mmol) were added at 0° C. to methanol (2.0 mL). The reaction mixture was stirred at room temperature for 3 hours, quenched with distilled water, and then extracted with ethyl acetate three times. The combined extract was washed with brine, dried on anhydrous magnesium sulfate, and then concentrated under reduced pressure to give 17.0 mg of the titled compound as a yellow liquid.
Reaction SMILES: [CH3:1][NH:2][C:3]1[C:7]([CH2:8][OH:9])=[CH:6][N:5]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:4]=1>[O-2].[O-2].[Mn+4].O1CCCC1>[CH3:1][NH:2][C:3]1[C:7]([CH:8]=[O:9])=[CH:6][N:5]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:4]=1
Reactant: CNc1nn(-c2ccccc2)cc1CO
Agent: [Mn+4]
Agent: [O-2]
Solvent: C1CCOC1
Product: CNc1nn(-c2ccccc2)cc1C=O
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A mixture of [3-(methylamino)-1-phenyl-1H-pyrazol-4-yl]methanol (15.42 g), activated manganese dioxide (50 g) and tetrahydrofuran (150 mL) was stirred at room temperature for 16 hrs. The obtained mixture was filtered, and the filtrate was concentrated. The residue was subjected to silica gel column chromatography to give 3-(methylamino)-1-phenyl-1H-pyrazole-4-carbaldehyde as colorless crystals from a fraction eluted with ethyl acetate-hexane (1:4, v/v). Recrystallization from ethyl acetate-hexane gave colorless needle crystal (9.17 g, yield 60%). melting point: 83-84° C.