Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][CH2:2][CH:3]1[O:7][C:6](=[O:8])[N:5]([C:9]2[CH:14]=[C:13]([F:15])[C:12]([C:16]3[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=3)=[C:11]([F:22])[CH:10]=2)[CH2:4]1.N1C=CC=CC=1.[C:29](OC(=O)C)(=[O:31])[CH3:30]>C(Cl)Cl>[C:29]([NH:1][CH2:2][CH:3]1[O:7][C:6](=[O:8])[N:5]([C:9]2[CH:10]=[C:11]([F:22])[C:12]([C:16]3[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=3)=[C:13]([F:15])[CH:14]=2)[CH2:4]1)(=[O:31])[CH3:30]
Reactant: CC(=O)OC(C)=O
Reactant: NCC1CN(c2cc(F)c(-c3cccnc3)c(F)c2)C(=O)O1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(=O)NCC1CN(c2cc(F)c(-c3cccnc3)c(F)c2)C(=O)O1

Procedure:
(±)-5-(Aminomethyl)-3-[4-(3-pyridyl)-3,5-difluorophenyl]-2-oxazolidinone (PREPARATION 7, 135 mg, 0.433 mmol) in anhydrous methylene chloride (10 ml), pyridine (143 μl, 1.77 mmol, 4 eq) and acetic anhydride (167 μl, 1.77 mmol, 4 eq) are combined. The reaction is allowed to stir at 20°-25° under nitrogen. After 2.5 hr the reaction is added to methylene chloride (30 ml) and washed with saturated sodium bicarbonate then brine, dried (sodium sulfate), filtered and concentrated under reduced pressure to a solid. This material is purified by silica gel (70 g) chromatography eluted with methanol/chloroform (1/99-4/96 gradient). The appropriate fractions are pooled and concentrated to give the title compound, mp 218°-219°; FTIR (mull) cm-1 3347, 1742, 1679, 1648, 1563, 1409, 1247, 1022, 755; MS (EI, m/z) 347 [M+ ], 303, 275, 244, 219, 73, 56; NMR (CDCl3) 8.68, 8.59, 7.85, 7.48-7.41, 7.31, 4.87-4.79, 4.10, 3.89., 3.72-3.57, 2.03 δ.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:17]=[C:18]([C:23]5[CH:28]=[CH:27][C:26]([CH2:29][NH:30][CH3:31])=[CH:25][CH:24]=5)[C:19]([CH3:22])=[CH:20][CH:21]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.[CH3:32][S:33](Cl)(=[O:35])=[O:34].CCN(CC)CC>CN(C)C=O>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[CH:17]=[C:18]([C:23]5[CH:24]=[CH:25][C:26]([CH2:29][N:30]([CH3:31])[S:33]([CH3:32])(=[O:35])=[O:34])=[CH:27][CH:28]=5)[C:19]([CH3:22])=[CH:20][CH:21]=4)=[O:14])[CH2:11][CH2:12]3)=[CH:9][C:4]=2[O:3][CH2:2]1
Reactant: CS(=O)(=O)Cl
Reactant: CNCc1ccc(-c2cc(NC(=O)C3(c4ccc5c(c4)OCO5)CC3)ccc2C)cc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cc1ccc(NC(=O)C2(c3ccc4c(c3)OCO4)CC2)cc1-c1ccc(CN(C)S(C)(=O)=O)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 63.8 %

Procedure:
1-(Benzo[d][1,3]dioxol-5-yl)-N-(6-methyl-4′-((methylamino)-methyl)biphenyl-3-yl)cyclopropane carboxamide (30 mg, 0.070 mmol), methanesulfonyl chloride (7.8 μL, 0.14 mmol) and Et3N (30 μL, 0.22 mmol) were dissolved in N,N-dimethylformamide (1.0 mL) and allowed to stir at 25° C. for 16 hours. The crude reaction was purified by reverse phase HPLC to afford 1-(benzo[d][1,3]dioxol-5-yl)-N-(6-methyl-4′-((N-methylmethylsulfonamido) methyl)biphenyl-3-yl)cyclopropanecarboxamide (22 mg, 64%). ESI-MS m/z calc. 492.2, found 493.3 (M+1)+; retention time 3.45 minutes.
Reaction SMILES: [CH2:1]([C:3]1[N:7]=[C:6]([C:8]2[S:12][C:11]([NH2:13])=[N:10][C:9]=2[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[O:5][N:4]=1)[CH3:2].[CH:20]1([C:26](Cl)=[O:27])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1>>[CH2:1]([C:3]1[N:7]=[C:6]([C:8]2[S:12][C:11]([NH:13][C:26]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)=[O:27])=[N:10][C:9]=2[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[O:5][N:4]=1)[CH3:2]
Reactant: O=C(Cl)C1CCCCC1
Reactant: CCc1noc(-c2sc(N)nc2-c2ccccc2)n1
Product: CCc1noc(-c2sc(NC(=O)C3CCCCC3)nc2-c2ccccc2)n1

Procedure:
Prepared from 5-(3-ethyl-[1,2,4]oxadiazol-5-yl)-4-phenyl-thiazol-2-ylamine and cyclohexanecarbonyl chloride.
Reaction SMILES: C([O:3][C:4](=O)[CH:5]=[C:6]([CH2:16][NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:7][NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])C.C(=O)=O.CC(C)=O.[H-]>O1CCCC1>[C:12]([O:11][C:9](=[O:10])[NH:8][CH2:7][C:6]([CH2:16][NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:5][CH2:4][OH:3])([CH3:14])([CH3:15])[CH3:13]
Reactant: CCOC(=O)C=C(CNC(=O)OC(C)(C)C)CNC(=O)OC(C)(C)C
Agent: O=C=O
Agent: [H-]
Solvent: CC(C)=O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NCC(=CCO)CNC(=O)OC(C)(C)C
Temperature: -78 °C
Reaction time: 2 h
Yield: 95.6 %

Procedure:
To a solution of 4-tert-butoxycarbonylamino-3-(tert-butoxycarbonylamino-methyl)-but-2-enoic acid ethyl ester (7.0 g, 19.5 mmol) in tetrahydrofuran (195 ml), at a reaction temperature of −78° C. (dry ice/acetone) was added a solution of diissobutylaluminum hydride (1 M in CH2Cl2, 59 ml, 59 mmol) and the reaction mixture stirred at −78° C. for 2 hours under a N2 atmosphere. The reaction was quenched with a saturated solution of sodium tartrate tetrahydrate (300 ml), stirred vigorously until the layers clarified then extracted with methylene chloride (2×100 ml). The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo to afford a yellow oil. Purification via column chromatography on silica gel (ethyl acetate:hexane, 1:1, v/v) afforded the product as a yellow oil (5.90 g, 96%). 1HNMR (CDCl3) δ 1.43 (s, 18H), 3.72 (s, 4H), 4.18 (t, 2H), 4.76 (s, 1H), 5.54 (s, 1H), 5.96 (t, 1H).
Reaction SMILES: [CH:1](NC(C)C)([CH3:3])[CH3:2].[Li].[N:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH2:15][CH:16]1[NH:20][C:19](=[O:21])[CH2:18][CH2:17]1.C(Br)CC.C(O)(=O)C>C1COCC1>[CH2:2]([CH:18]1[CH2:17][CH:16]([CH2:15][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][N:9]=2)[NH:20][C:19]1=[O:21])[CH2:1][CH3:3]
Reactant: CC(C)NC(C)C
Reactant: O=C1CCC(Cc2ccccn2)N1
Agent: [Li]
Solvent: CCCBr
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: CCCC1CC(Cc2ccccn2)NC1=O
Temperature: -78 °C
Reaction time: 1.5 h

Procedure:
To a 2 M lithium diisopropylamine solution in THF of −78° C. is added 5-(pyridin-2-ylmethyl)pyrrolidin-2-one, and the mixture is stirred for 1.5 hours at −78° C. Then 1-propyl bromide is added and the reaction is stirred for another 1.5 hours at −78° C. The reaction mixture is allowed to warm up to 0° C. before ice-cold water with acetic acid is added and subsequently extracted 3 times with dichloromethane. The dichloromethane is concentrated in vacuo and the residue is dissolved in dichloromethane, washed with saturated NaHCO3 and brine. Crude 3-propyl-5-(pyridin-2-ylmethyl)pyrrolidin-2-one is obtained after removal of the solvents in vacuo. The product is purified by column chromatography.
Reaction SMILES: Br[C:2]1[N:3]=[CH:4][C:5]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[C:21]([CH3:22])=[CH:20][C:19]([CH:23]4[CH2:25][CH2:24]4)=[CH:18][N:17]=3)[CH2:12][CH2:11]2)=[O:9])=[N:6][CH:7]=1.[CH2:26]([C@@H:28]1[CH2:32][O:31][C:30](=[O:33])[NH:29]1)[CH3:27]>>[CH:23]1([C:19]2[CH:20]=[C:21]([CH3:22])[C:16]([N:13]3[CH2:14][CH2:15][N:10]([C:8]([C:5]4[N:6]=[CH:7][C:2]([N:29]5[C@H:28]([CH2:26][CH3:27])[CH2:32][O:31][C:30]5=[O:33])=[N:3][CH:4]=4)=[O:9])[CH2:11][CH2:12]3)=[N:17][CH:18]=2)[CH2:25][CH2:24]1
Reactant: Cc1cc(C2CC2)cnc1N1CCN(C(=O)c2cnc(Br)cn2)CC1
Reactant: CC[C@@H]1COC(=O)N1
Product: CC[C@@H]1COC(=O)N1c1cnc(C(=O)N2CCN(c3ncc(C4CC4)cc3C)CC2)cn1
Yield: 31.5 %

Procedure:
Using (5-bromopyrazin-2-yl)[4-(5-cyclopropyl-3-methylpyridin-2-yl)piperazin-1-yl]methanone (158 mg) described in Preparation Example 243 and (R)-4-ethyloxazolidin-2-one (68 mg) and by the reaction and treatment in the same manner as in Example 1, the title compound (54 mg) was obtained.
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]([C:13]2[CH2:14][CH2:15][NH:16][CH2:17][CH:18]=2)[CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11].Cl.Br[CH:21]([CH3:25])[C:22]([NH2:24])=[O:23].C(=O)([O-])[O-].[Cs+].[Cs+].C(#N)C>>[CH3:2][O:3][C:4]1[CH:5]=[C:6]([C:13]2[CH2:18][CH2:17][N:16]([CH:21]([CH3:25])[C:22]([NH2:24])=[O:23])[CH2:15][CH:14]=2)[CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11]
Reactant: CC(Br)C(N)=O
Reactant: COc1cc(C2=CCNCC2)ccc1[N+](=O)[O-]
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC#N
Product: COc1cc(C2=CCN(C(C)C(N)=O)CC2)ccc1[N+](=O)[O-]
Temperature: 25 °C

Procedure:
A mixture of 4-(3-Methoxy-4-nitro-phenyl)-1,2,3,6-tetrahydro-pyridine hydrochloride (364 mg, 1.34 mmol) (generated by 4N HCl treatment of the of BOC precursor, 450 mg, for 1 h), 2-Bromo-propionamide (204 mg, 1.34 mmol), and cesium carbonate (1095 mg, 3.362 mmol) in acetonitrile (10 mL, 200 mmol) was stirred overnight at reflux. The mixture was cooled to RT and was filtered through a pad of celite. After solvent evaporation and flash chromatography (ISCO, EtOAC: MeOH 98:3), the product, 2-[4-(3-Methoxy-4-nitro-phenyl)-3,6-dihydro-2H-pyridin-1-yl]-propionamide was isolated as a gum (101 mg, 25%). MS: 306 (M+H).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=2)=[CH:9]/[CH:10]=[CH:11]/[C:12]([OH:14])=[O:13])=[CH:4][CH:3]=1.[N+:22]([C:25]1[CH:30]=[CH:29][C:28](O)=[CH:27][CH:26]=1)([O-:24])=[O:23].C1(N=C=NC2CCCCC2)CCCCC1>ClCCl>[N+:22]([C:25]1[CH:30]=[CH:29][C:28]([O:13][C:12](=[O:14])/[CH:11]=[CH:10]/[CH:9]=[C:8]([C:5]2[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=2)[C:15]2[CH:16]=[CH:17][C:18]([CH3:21])=[CH:19][CH:20]=2)=[CH:27][CH:26]=1)([O-:24])=[O:23]
Reactant: Cc1ccc(C(=C/C=C/C(=O)O)c2ccc(C)cc2)cc1
Reactant: O=[N+]([O-])c1ccc(O)cc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: ClCCl
Product: Cc1ccc(C(=C/C=C/C(=O)Oc2ccc([N+](=O)[O-])cc2)c2ccc(C)cc2)cc1
Reaction time: 0.5 h
Yield: 85.5 %

Procedure:
As in Example 115, (E)-5,5-bis(4-methylphenyl)-2,4-pentadienoic acid (7.25 g) and 4-nitrophenol (4.4 g) in dichloromethane (60 mL) was treated with 1,3-dicyclohexylcarbodiimide (5.36 g). The mixture was stirred at 0°-5° C. for 30 minutes and then at room temperature for 18 hours. After the usual work up, the ester was crystallized from 2-propanol to yield 8.9 g of (E)-5,5-bis(4-methylphenyl)-2,4-pentadienoic acid 4-nitrophenyl ester, mp 153.5°-154.5° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:13]=[C:14]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[C:15]([OH:17])=O)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].[CH2:25]([O:27][C:28](=[O:37])[C:29]1[CH:34]=[CH:33][C:32]([CH2:35][NH2:36])=[CH:31][CH:30]=1)[CH3:26].Cl.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[F:24][C:21]1[CH:22]=[CH:23][C:18]([C:14](=[CH:13][C:5]2[CH:6]=[C:7]([O:11][CH3:12])[C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=2)[C:15]([NH:36][CH2:35][C:32]2[CH:31]=[CH:30][C:29]([C:28]([O:27][CH2:25][CH3:26])=[O:37])=[CH:34][CH:33]=2)=[O:17])=[CH:19][CH:20]=1
Reactant: COc1cc(C=C(C(=O)O)c2ccc(F)cc2)cc(OC)c1OC
Reactant: CCOC(=O)c1ccc(CN)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: CCOC(=O)c1ccc(CNC(=O)C(=Cc2cc(OC)c(OC)c(OC)c2)c2ccc(F)cc2)cc1
Yield: 50 %

Procedure:
To a solution of 3-(3,4,5-trimethoxyphenyl)-2-(4-fluorophenyl)acrylic acid (0.6 g, 18 mmol) in DMF (5 mL) was added ethyl-4-aminomethylbenzoate.HCl (0.375 g, 21.6 mmol), EDCI (0.69 g, 36 mmol) and HOBt (0.24 g, 18 mmol). TEA (0.75 mL, 36 mmol) was added dropwise with constant stirring to the above reaction mixture and stirred overnight at room temperature. Subsequently the reaction mixture was evaporated to dryness, the residue was dissolved in ethyl acetate and washed successively with 1N HCl (3×50 mL), saturated NaHCO3 (3×50 mL) and brine solution (3×50 mL). The organic layer was dried over Na2SO4 and concentrated to give the pure compound (0.4 g, 50% yield).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[N:11]3[N:18]=[CH:19][C:20]([C:21](O)=[O:22])=[C:10]3[N:9]=2)=[CH:4][CH:3]=1.[NH2:24][C:25]1[CH:34]=[CH:33][C:28]([C:29]([NH:31]O)=[NH:30])=[CH:27][N:26]=1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[N:11]3[N:18]=[CH:19][C:20]([C:21]4[O:22][N:31]=[C:29]([C:28]5[CH:33]=[CH:34][C:25]([NH2:24])=[N:26][CH:27]=5)[N:30]=4)=[C:10]3[N:9]=2)=[CH:4][CH:3]=1
Reactant: N=C(NO)c1ccc(N)nc1
Reactant: O=C(O)c1cnn2c(C(F)(F)F)cc(-c3ccc(Cl)cc3)nc12
Product: Nc1ccc(-c2noc(-c3cnn4c(C(F)(F)F)cc(-c5ccc(Cl)cc5)nc34)n2)cn1

Procedure:
The title compound was prepared from 5-(4-chloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C.4) (171 mg, 0.5 mmol) and 6-amino-N-hydroxy-nicotinamidine (example B.4) (114 mg, 0.75 mmol) according to general procedure II. Obtained after flash chromatography on silica gel (ethyl acetate/heptane) and further purification by crystallization (dichloromethane/hexane) as a yellow solid (81 mg, 36%). MS (ISP) 458.1 [(M+H)+]; mp 253° C.
Reaction SMILES: [C:1]1([CH3:20])[CH:6]=[CH:5][C:4]([S:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([OH:16])=[O:15])[C:9]=2[C:17]([OH:19])=O)=[CH:3][CH:2]=1.ClS(O)(=O)=O>O>[CH3:20][C:1]1[CH:2]=[C:3]2[C:4]([S:7][C:8]3[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([OH:16])=[O:15])[C:9]=3[C:17]2=[O:19])=[CH:5][CH:6]=1
Reactant: Cc1ccc(Sc2cccc(C(=O)O)c2C(=O)O)cc1
Agent: O=S(=O)(O)Cl
Solvent: O
Product: Cc1ccc2sc3cccc(C(=O)O)c3c(=O)c2c1
Yield: 87.7 %

Procedure:
The 3-(p-tolylthio)benzene-1,2-dicarboxylic acid is slowly added to 18 g of chlorosulfonic acid cooling at 5 and 10° C. with an ice-bath. After 1 hour the mixture is poured in iced water. The precipitate is filtered, washed with water and dried obtaining 1.20 g (87.7%) of 7-methyl-9-oxo-9H-thioxanthene-1-carboxylic acid as a yellow solid.
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[C:9]([CH:13]=[CH:14][C:15]=2[OH:16])[C:10]([OH:12])=[O:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].[C:19](OC(=O)C)(=[O:21])[CH3:20].Cl>O>[C:1]1([C:7]2[CH:8]=[C:9]([CH:13]=[CH:14][C:15]=2[O:16][C:19](=[O:21])[CH3:20])[C:10]([OH:12])=[O:11])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC(=O)OC(C)=O
Reactant: O=C(O)c1ccc(O)c(-c2ccccc2)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC(=O)Oc1ccc(C(=O)O)cc1-c1ccccc1

Procedure:
A solution of 3-phenyl-4-hydroxybenzoic acid (131.1 g, 0.061 mole) and a 50 weight percent aqueous solution of NaOH (10.5 g, 0.131 mole) in 350 ml of deionized water was added to a 500 ml, three-necked, round-bottom flask equipped with a thermometer and a polytetrafluoroethylene-coated magnetic stir bar. The solution was stirred to homogeneity and then immersed in an ice water bath. With the solution temperature at 10° C., acetic anhydride (12.7 g, 0.124 mole) was added rapidly with stirring. Immediately, a white precipitate began to form. The reaction mixture was stirred for one hour at 10° C., then neutralized with concentrated HCl. The precipitate was filtered, washed in 500 ml of deionized water for one hour, filtered, and dried in an 80° C. vacuum oven for three hours yielding an off-white solid. The solid was recrystallized from a toluene and hexane mixture to give a fluffy white solid, 3-phenyl-4-acetoxybenzoic acid with a m.p. of 185° C. to 187° C.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]([C:10]([OH:12])=[O:11])[CH2:2]1.C(N(CC)C(C)C)(C)C.[CH3:22][O:23][C:24]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27]([S:34](Cl)(=[O:36])=[O:35])=[CH:26][CH:25]=1.C(=O)(O)[O-].[Na+]>CN(C)C=O>[CH3:22][O:23][C:24]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27]([S:34]([N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH:3]([C:10]([OH:12])=[O:11])[CH2:2]2)(=[O:36])=[O:35])=[CH:26][CH:25]=1
Reactant: O=C(O)C1CNc2ccccc21
Reactant: COc1ccc(S(=O)(=O)Cl)c2ccccc12
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc(S(=O)(=O)N2CC(C(=O)O)c3ccccc32)c2ccccc12
Yield: 73.2 %

Procedure:
To 2,3-dihydro-1H-indole-3-carboxylic acid (A) (3.59 g, 22.0 mmol) was added aqueous N,N-dimethylformamide (DMF) (3:2 v/v; 75 cm3), and then N,N-diisopropylethylamine (9.0 cm3, 50.7 mmol). The mixture was stirred at room temperature for 5 min, before 4-methoxy-1-naphthyl sulfonyl chloride (B)(5.64 g, 22.0 mmol) was added. After stirring for a further 16 h at room temperature saturated aqueous sodium bicarbonate (60 cm3) was added and the organic material was extracted into ethyl acetate (60 cm3). The organic layer was then washed with a further portion of saturated aqueous sodium bicarbonate (40 cm3) before the aqueous fractions were combined and acidified to pH 5 with 5N hydrochloric acid. The desired material was then extracted from the acidified aqueous mixture into ethyl acetate (2×60 cm3), which was subsequently dried over sodium sulfate and evaporated under reduced pressure to afford the title compound (C) (6.1 g, 16.1 mmol, 73%).
Reaction SMILES: [NH2:1][C@@H:2]1[C:14](=[O:15])[N:4]2[C:5]([C:11]([OH:13])=[O:12])=[C:6]([CH:9]=[CH2:10])[CH2:7][S:8][C@H:3]12.C[Si](C)(C)NC(=O)C.[NH2:24][C:25]1[S:26][C:27]([Cl:39])=[C:28](/[C:30](=[N:34]/[O:35]C(=O)C)/[C:31](Cl)=[O:32])[N:29]=1.CO>ClCCl>[NH2:24][C:25]1[S:26][C:27]([Cl:39])=[C:28](/[C:30](=[N:34]/[OH:35])/[C:31]([NH:1][C@@H:2]2[C:14](=[O:15])[N:4]3[C:5]([C:11]([OH:13])=[O:12])=[C:6]([CH:9]=[CH2:10])[CH2:7][S:8][C@H:3]23)=[O:32])[N:29]=1
Reactant: C=CC1=C(C(=O)O)N2C(=O)[C@@H](N)[C@H]2SC1
Reactant: CC(=O)O/N=C(\C(=O)Cl)c1nc(N)sc1Cl
Agent: CC(=O)N[Si](C)(C)C
Solvent: ClCCl
Solvent: CO
Product: C=CC1=C(C(=O)O)N2C(=O)[C@@H](NC(=O)/C(=N\O)c3nc(N)sc3Cl)[C@H]2SC1
Reaction time: 1 h
Yield: 7.2 %

Procedure:
To a solution of 7β-amino-3-vinyl-3-cephem-4-carboxylic acid (1 g) and N-(trimethylsilyl)acetamide (5.8 g) in dichloromethane (10 ml) was added 2-(2-amino-5-chlorothiazol-4-yl)-2-(Z)-(acetoxyimino)acetyl chloride (1.69 g) under ice-cooling. After being stirred at the same temperature for 1 hour, to this mixture was added methanol (10 ml). After evaporating in vacuo to remove the dichloromethane, the residue was added conc. hydrochloric acid (1.95 ml) at room temperature. After being stirred at the same temperature for 4 hours, the mixture was poured into water (10 ml). The mixture was adjusted to pH 3.5 with 28% ammonium hydroxide in water, and the resulting precipitate was collected by filtration to afford 7β-[2-(2-amino-5-chlorothiazol-4-yl)-2-(Z)-(hydroxyimino)acetamido]-3-vinyl-3-cephem-4-carboxylic acid (137 mg).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:23])[CH2:5][N:6]([CH:20]1[CH2:22][CH2:21]1)[C:7](=[O:19])[C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=1)[CH3:2].[CH2:24]([N:31]([CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C:32]1[CH:40]=[CH:39][C:35]([C:36](O)=[O:37])=[CH:34][N:33]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>>[CH2:1]([O:3][C:4](=[O:23])[CH:5]([N:6]([CH:20]1[CH2:22][CH2:21]1)[C:7](=[O:19])[C:8]1[CH:9]=[CH:10][C:11]([O:14][C:15]([F:16])([F:17])[F:18])=[CH:12][CH:13]=1)[C:36]([C:35]1[CH:34]=[N:33][C:32]([N:31]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[CH:40][CH:39]=1)=[O:37])[CH3:2]
Reactant: CCOC(=O)CN(C(=O)c1ccc(OC(F)(F)F)cc1)C1CC1
Reactant: O=C(O)c1ccc(N(Cc2ccccc2)Cc2ccccc2)nc1
Product: CCOC(=O)C(C(=O)c1ccc(N(Cc2ccccc2)Cc2ccccc2)nc1)N(C(=O)c1ccc(OC(F)(F)F)cc1)C1CC1

Procedure:
The title compound, a colorless oil (0.7 g, 32%), was prepared in analogy to intermediate 8A by reaction of [cyclopropyl-(4-trifluoromethoxy-benzoyl)-amino]-acetic acid ethyl ester (intermediate 7B) with 6-dibenzylamino-nicotinic acid (Aminopyridines. Jpn. Kokai Tokkyo Koho (1979), JP54041881). MS: 632.3 (MH+).
Reaction SMILES: CO[C:3]1[CH:9]=[C:8]([N:10]2[CH2:14][CH2:13][CH2:12]C2)C=CC=1N.F[C:16]1[CH:17]=[CH:18][C:19]([N+:26]([O-])=O)=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:21]=1.CC1CCCNC1.CC#N>O>[CH3:12][CH:13]1[CH2:3][CH2:9][CH2:8][N:10]([C:16]2[CH:17]=[CH:18][C:19]([NH2:26])=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:21]=2)[CH2:14]1
Reactant: COc1cc(N2CCCC2)ccc1N
Reactant: O=[N+]([O-])c1ccc(F)cc1C(F)(F)F
Agent: CC1CCCNC1
Solvent: O
Solvent: CC#N
Product: CC1CCCN(c2ccc(N)c(C(F)(F)F)c2)C1

Procedure:
2-Methoxy-4-(pyrrolidin-1-yl)aniline can be synthesized following the general scheme above starting from 5-fluoro-2-nitrobenzotrifluoride and 3-methylpiperidine. 1H NMR (400 MHz, CDCl3) δ 7.05-6.93 (m, 2H), 6.69 (d, J=8.7 Hz, 1H), 3.85 (s, 2H), 3.42-3.29 (m, 2H), 2.52 (td, J=11.5, 3.1 Hz, 1H), 2.25-2.15 (m, 1H), 1.86-1.62 (m, 5H), 0.94 (d, J=6.4 Hz, 3H). LC/MS: m/z 259.0 (M+H)+ at 0.79 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).
Reaction SMILES: C=CCCCCCCCC.COC(=O)CCCCCCCC=C.[C:24](OC)(=O)[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]/[CH:32]=[CH:33]\[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41]>>[CH3:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH:32]=[CH:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)OC
Agent: C=CCCCCCCCC
Agent: C=CCCCCCCCC(=O)OC
Product: CCCCCCCCC=CCCCCCCCC

Procedure:
In a particular embodiment, the metathesis of methyl oleate with ethylene will yield cross-metathesis products of 1-decene and methyl-9-decenoate. In addition to the desired products, the methyl oleate may homometathesize to produce small amounts of 9-octadecene, a less desirable product, and 1,18-dimethyl-9-octadecenedioate, a second less desirable product. Yield was calculated as 100×[micromoles of ethenolysis products obtained from the GC]/[micromoles of methyl oleate weighed into reactor]. 1-decene selectivity is shown as a percentage and was calculated as 100×[GC peak area of 1-decene & methyl-9-decenoate]/[sum of GC peak areas of 1-decene, methyl-9-decenoate, and the homometathesis products, 9-octadecene, and 1,18-dimethyl-9-octadecenedioate]. Catalyst turnovers for production of the 1-decene was calculated as the [micromoles of 1-decene obtained from the gas chromatograph]/([micromoles of catalyst].
Reaction SMILES: [CH3:1][N:2]1[C:6]2=[N:7][C:8]([S:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[CH:9][CH:10]=[C:5]2[N:4]=[C:3]1[CH2:18][O:19][C:20]1[CH:52]=[CH:51][C:23]([CH2:24][CH:25]2[S:29][C:28](=[O:30])[N:27](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[C:26]2=[O:50])=[CH:22][CH:21]=1.C(O)(=O)C>O>[CH3:1][N:2]1[C:6]2=[N:7][C:8]([S:11][C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)=[CH:9][CH:10]=[C:5]2[N:4]=[C:3]1[CH2:18][O:19][C:20]1[CH:52]=[CH:51][C:23]([CH2:24][CH:25]2[S:29][C:28](=[O:30])[NH:27][C:26]2=[O:50])=[CH:22][CH:21]=1
Reactant: Cn1c(COc2ccc(CC3SC(=O)N(C(c4ccccc4)(c4ccccc4)c4ccccc4)C3=O)cc2)nc2ccc(Sc3ccccc3)nc21
Solvent: CC(=O)O
Solvent: O
Product: Cn1c(COc2ccc(CC3SC(=O)NC3=O)cc2)nc2ccc(Sc3ccccc3)nc21
Yield: 97.4 %

Procedure:
A procedure similar to that described in Example 12 was repeated, except that 1.58 g of 5-[4-(3-methyl-5-phenylthioimidazo[5,4-b]pyridin-2-ylmethoxy)benzyl]-3-triphenylmethylthiazolidine-2,4-dione (prepared as described in Preparation 91) were treated with 20 ml of a 3:1 by volume mixture of acetic acid and water. After working up the product as described in Example 12, the resulting crude product was crystallized by trituration with ethyl acetate, to give 1.02 g of the title compound, melting at 166°-168° C.
Reaction SMILES: [C:1]([O:4][C:5]1[CH:10]=[C:9]([OH:11])[C:8]([Cl:12])=[CH:7][N:6]=1)(=[O:3])[CH3:2].[C:13](Cl)(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(N(CC)CC)C>C(#N)C>[C:1]([O:4][C:5]1[CH:10]=[C:9]([O:11][C:13](=[O:20])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]([Cl:12])=[CH:7][N:6]=1)(=[O:3])[CH3:2]
Reactant: O=C(Cl)c1ccccc1
Reactant: CC(=O)Oc1cc(O)c(Cl)cn1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CC(=O)Oc1cc(OC(=O)c2ccccc2)c(Cl)cn1
Yield: 96 %

Procedure:
The general procedure of Example 21 was followed using 200 mg of 2-acetoxy-5-chloro-4-hydroxypyridine, 0.15 ml of benzoyl chloride and 0.74 ml of triethylamine and 20 ml of acetonitrile, thereby giving 300 mg of the title compound in a yield of 96%.
Reaction SMILES: Br[C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][N:8]2[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:4][CH:3]=1.[CH2:18]([Sn](CCCC)(CCCC)C=C)[CH2:19]CC.CC1C=CC=C(C)C=1CN1C2C(=CC=C(C(O)=O)C=2)C=C1>>[CH:18]([C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][N:8]2[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:4][CH:3]=1)=[CH2:19]
Reactant: CC(C)(C)OC(=O)N1CCc2ccc(Br)cc21
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Agent: Cc1cccc(C)c1Cn1ccc2ccc(C(=O)O)cc21
Product: C=Cc1ccc2c(c1)N(C(=O)OC(C)(C)C)CC2

Procedure:
The titled compound (207 mg) as a white solid was prepared from tert-butyl 6-bromo-2,3-dihydro-1H-indole-1-carboxylate obtained by the method described in the document (WO 1998/43956 A) and tributyl(vinyl)tin according to the method of the process (2) of Example 66.