Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([CH:8]1[CH2:13][CH2:12][N:11]([C:14]2[NH:15][C:16]3[C:21]([CH:22]=2)=[CH:20][C:19]([C:23]([NH2:25])=[O:24])=[CH:18][CH:17]=3)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[K+].[C:28](Cl)(=[O:31])[CH:29]=[CH2:30]>CC(C)=O>[C:28]([N:15]1[C:16]2[C:21](=[CH:20][C:19]([C:23]([NH2:25])=[O:24])=[CH:18][CH:17]=2)[CH:22]=[C:14]1[N:11]1[CH2:10][CH2:9][CH:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:13][CH2:12]1)(=[O:31])[CH:29]=[CH2:30]
Reactant: C=CC(=O)Cl
Reactant: NC(=O)c1ccc2[nH]c(N3CCC(Cc4ccccc4)CC3)cc2c1
Agent: [K+]
Agent: [OH-]
Solvent: CC(C)=O
Product: C=CC(=O)n1c(N2CCC(Cc3ccccc3)CC2)cc2cc(C(N)=O)ccc21

Procedure:
0.318 g (1 mmol) of (4-benzylpiperidinyl)-indole-5-carboxamide was taken in 15 mL dry acetone and was reacted with 0.2 g (5 mmol) of powdered KOH for 15 Min. The mixture was cooled in ice and 0.225 mg (2.5 mmol) of acryloyl chloride was added in one lot. Stirring continued at 0° C. for 20 Min., after which the reaction was further stirred at room temp. for 1 h. the solvent was removed in vacuo and the residue was extracted with ethyl acetate from water. The extract was dried and evaporated. TLC (ethyl acetate-hexane) and mass spectrum (M+ at 372) confirmed the desired product. This product was used without further purification for the next step.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:7][C:8]([CH3:48])=[C:9]([CH2:11][O:12][C:13]2[CH:47]=[CH:46][C:16]([CH2:17][N:18]3[CH:22]=[C:21]([CH2:23][OH:24])[C:20]([O:25][CH2:26][C:27]4[CH:32]=[CH:31][C:30]([O:33][CH2:34][C:35]5[N:36]=[C:37]([C:41]6[O:42][CH:43]=[CH:44][CH:45]=6)[O:38][C:39]=5[CH3:40])=[CH:29][CH:28]=4)=[N:19]3)=[CH:15][CH:14]=2)[N:10]=1>[O-2].[O-2].[Mn+4].O1CCCC1>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:7][C:8]([CH3:48])=[C:9]([CH2:11][O:12][C:13]2[CH:14]=[CH:15][C:16]([CH2:17][N:18]3[CH:22]=[C:21]([CH:23]=[O:24])[C:20]([O:25][CH2:26][C:27]4[CH:28]=[CH:29][C:30]([O:33][CH2:34][C:35]5[N:36]=[C:37]([C:41]6[O:42][CH:43]=[CH:44][CH:45]=6)[O:38][C:39]=5[CH3:40])=[CH:31][CH:32]=4)=[N:19]3)=[CH:46][CH:47]=2)[N:10]=1
Reactant: Cc1oc(-c2ccco2)nc1COc1ccc(COc2nn(Cc3ccc(OCc4nc(-c5ccco5)oc4C)cc3)cc2CO)cc1
Agent: [Mn+4]
Agent: [O-2]
Solvent: C1CCOC1
Product: Cc1oc(-c2ccco2)nc1COc1ccc(COc2nn(Cc3ccc(OCc4nc(-c5ccco5)oc4C)cc3)cc2C=O)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 89.1 %

Procedure:
A mixture of [1-[4-[2-(2-furyl)-5-methyl-4-oxazolylmethoxy]benzyl]-3-[4-[2-(2-furyl)-5-methyl-4-oxazolylmethoxy]benzyloxy]-1H-pyrazol-4-yl]methanol (16.59 g), activated manganese dioxide (35.19 g) and tetrahydrofuran (100 ml) was stirred at room temperature for 3 hours. After the manganese dioxide was removed by filtration, the filtrate was concentrated. The crystals obtained were collected by filtration to yield 1-[4-[2-(2-furyl)-5-methyl-4-oxazolylmethoxy]benzyl]-3-[4-[2-(2-furyl)-5-methyl-4-oxazolylmethoxy]benzyloxy]-1H-pyrazole-4-carbaldehyde (14.73 g, yield: 89%). This was recrystallized from ethyl acetate-hexane. Melting point: 109–110° C.
Reaction SMILES: [Cl:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:23])[C:12]3[S:19][C:18]([CH2:20]Cl)=[C:17]([CH3:22])[C:13]=3[N:14]([CH3:16])[CH:15]=2)=[O:9])=[CH:4][CH:3]=1.[OH:26][CH:27]([C:31]1[CH:36]=[CH:35][C:34]([S:37]([NH2:40])(=[O:39])=[O:38])=[CH:33][CH:32]=1)[CH2:28][NH:29][CH3:30].C(N(C(C)C)CC)(C)C>CN(C=O)C.O>[NH2:40][S:37]([C:34]1[CH:33]=[CH:32][C:31]([CH:27]([OH:26])[CH2:28][N:29]([CH2:20][C:18]2[S:19][C:12]3[C:11](=[O:23])[C:10]([C:8]([NH:7][CH2:6][C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:25][CH:24]=4)=[O:9])=[CH:15][N:14]([CH3:16])[C:13]=3[C:17]=2[CH3:22])[CH3:30])=[CH:36][CH:35]=1)(=[O:38])=[O:39]
Reactant: Cc1c(CCl)sc2c(=O)c(C(=O)NCc3ccc(Cl)cc3)cn(C)c12
Reactant: CNCC(O)c1ccc(S(N)(=O)=O)cc1
Solvent: CN(C)C=O
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1c(CN(C)CC(O)c2ccc(S(N)(=O)=O)cc2)sc2c(=O)c(C(=O)NCc3ccc(Cl)cc3)cn(C)c12
Temperature: 25 °C
Reaction time: 72 h
Yield: 46.8 %

Procedure:
A mixture of N-(4-chlorobenzyl)-2-(chloromethyl)-3,4-dimethyl-7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamide (100 mg, 0.25 mmol), 4-[1-hydroxy-2-(methylamino)ethyl]benzenesulfonamide (Preparation 48)(60 mg, 0.26 mmol) and diisopropylethylamine (67 μL, 0.38 mmol) in dry DMF (5.0 mL) was stirred for 72 hours at room temperature. The solution was diluted with water (15 mL). The resulting milky suspension was stirred vigorously for 30 minutes, and then left standing overnight at room temp. The mixture was filtered, and the collected solid was washed with water and dried in vacuo, leaving a white solid. Recrystallization from acetonitrile (5 mL, dissolved with warming and then cooled to 0° C. overnight) gave the title compound (69 mg) as a white solid.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6](O)[CH:5]=[CH:4][N:3]=1.[F:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16]N)=[CH:12][CH:11]=1.C(O)(C)C.C1(C)C=CC=CC=1>C1(OC2C=CC=CC=2)C=CC=CC=1>[F:9][C:10]1[CH:15]=[CH:14][C:13]2[NH:16][C:6]3[CH:5]=[CH:4][NH:3][C:2](=[O:1])[C:7]=3[C:12]=2[CH:11]=1
Reactant: Oc1ccnc(O)c1
Reactant: NNc1ccc(F)cc1
Solvent: Cc1ccccc1
Solvent: CC(C)O
Solvent: c1ccc(Oc2ccccc2)cc1
Product: O=c1[nH]ccc2[nH]c3ccc(F)cc3c12
Temperature: 165 °C
Reaction time: 1 h

Procedure:
To 2,4-dihydroxypyridine (43.6 g, 392 mmol) in phenyl ether (760 mL) in a three neck flask fitted with a Dean-Stark trap was added 4-fluorophenylhydrazine in phenyl ether (100 mL). The reaction mixture was heated to 165° C. for 1 h, slowly warmed to 230° C., and left to stir at 230° C. for 1 h. The reaction mixture was allowed to cool to 45° C. and treated with isopropanol and toluene. The mixture was filtered, washed with toluene, and dried to give the title compound. 1H NMR (600 MHz, CD3SOCD3) δ 11.82 (s, 1H); 11.13 (s, 1H); 7.71 (dd, 1H); 7.45 (dd, 1H); 7.28 (t, 1H); 7.12 (m, 1H); 6.45 (d, 1H). LRMS (APCI) calc'd for (C11H7FN2O) [M+H]+, 203.1. found 203.1.
Reaction SMILES: N[C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5](SC2C(C)=C(S(O)(=O)=O)C(C)=C(N)C=2C)=[CH:4][C:3]=1S(O)(=O)=O.NC1C=C(S(O)(=O)=O)C=CC=1>>[CH:9]1[C:8]2[C:7](=[O:17])[C:6]3[C:15](=[CH:2][CH:3]=[CH:4][CH:5]=3)[C:14](=[O:16])[C:13]=2[CH:12]=[CH:11][CH:10]=1
Reactant: Cc1c(N)c(C)c(S(=O)(=O)O)c(C)c1Sc1cc(S(=O)(=O)O)c(N)c2c1C(=O)c1ccccc1C2=O
Agent: Nc1cccc(S(=O)(=O)O)c1
Product: O=C1c2ccccc2C(=O)c2ccccc21

Procedure:
Example 25 was repeated, except that the compounds shown in 1st, 2nd and 3rd columns of the following table were used in place of the 1-amino-4-(3'-amino-2',4',6'-trimethyl-5'-sulfophenylthio)anthraquinone-2-sulfonic acid, 1-aminobenzene-3-β-sulfatoethylsulfone and 3-aminobenzenesulfonic acid, respectively, thereby obtaining a corresponding anthraquinone compound. The color shade on cotton of the compound is as shown in a 4th column of the table.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([S:11](Cl)(=[O:13])=[O:12])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[N:15]1C=CC=C[CH:16]=1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:15][CH3:16])(=[O:13])=[O:12])=[CH:7][CH:6]=1)(=[O:3])[CH3:2]
Reactant: c1ccncc1
Reactant: CC(=O)Nc1ccc(S(=O)(=O)Cl)cc1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CNS(=O)(=O)c1ccc(NC(C)=O)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 82.5 %

Procedure:
To a cold (0° C.) suspension of 4-acetamido-benzenesulphonyl chloride (4.0 g, 17 mmol) in CH2Cl2 (40 mL) was added pyridine (1.7 mL, 20 mmol) and DMAP (209 mg, 1.7 mmol). (A clear solution resulted). Anhydrous methylamine was bubbled into the solution for 1 hour at 0° C., and then the solution was allowed to stir at 25° C. for 2 hours. The solution was extracted with 1M NaOH (3×15 mL) and the combined extracts were adjusted to pH 6 at 0° C. with 3M HCl. The product, which precipitated as fluffy white crystals, was filtered and washed with cold water to afford 3.2 g (82%) of 4-acetamido-N-methylbenzenesulphonamide: 1H NMR (300 MHz, MeOH) δ 2.35 (s,3H), 2.70 (s,3H), 7.96 (s,4H).
Reaction SMILES: CO.CCCCCC.C(OCC)(=O)C.[CH3:15][C:16]1[CH:21]([OH:22])[C:20]([CH3:27])([C:23]([F:26])([F:25])[F:24])[CH2:19][C:18](=[O:28])[CH:17]=1>CC(C)=O.CC(C)=O.OS(O)(=O)=O.O=[Cr](=O)=O>[CH3:15][C:16]1[C:21](=[O:22])[C:20]([CH3:27])([C:23]([F:24])([F:25])[F:26])[CH2:19][C:18](=[O:28])[CH:17]=1
Reactant: CC1=CC(=O)CC(C)(C(F)(F)F)C1O
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: CC(C)=O
Solvent: CO
Solvent: CCCCCC
Product: CC1=CC(=O)CC(C)(C(F)(F)F)C1=O
Reaction time: 0.17 h
Yield: 86.4 %

Procedure:
In the 20 ml of acetone was dissolved 3,5-dimethyl-5-trifluoromethyl-4-hydroxy-2-cyclohexen-1-one(A-4) prepared in Example 5, and 6.2 ml of Jones reagent was added dropwise. Then, the mixture was stirred for 10 minutes, was added dropwise to 10 ml of methyl alcohol and stirred for 30 minutes. The reaction mixture was filtered to remove the filtrate. The residue thus obtained was fractionated with column chromatography using n-hexane/ethyl acetate(4:1, v/v) as eluent to give 2.74 g of the title compound(yield: 86.4%).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1.Br[CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13]>CN(C=O)C.CC(=O)OCC>[OH:9][C:6]1[CH:7]=[CH:8][C:3]([CH2:2][NH:1][CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[CH:4][CH:5]=1
Reactant: CC(C)(C)OC(=O)CBr
Reactant: NCc1ccc(O)cc1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)CNCc1ccc(O)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 48.4 %

Procedure:
Prepared using General Procedure 13: To a stirred solution of 4-(aminomethyl)phenol (2.0 g, 16.2 mmol) in DMF (10 mL) was added TEA (4.53 mL, 32.5 mmol) followed by tert-butyl 2-bromoacetate (2.40 mL, 16.2 mmol) added drop-wise over 30 minutes. After stirring a further 1 h at room temperature, the reaction mixture was diluted with EA (100 mL) and washed with water (2×100 mL). The organics were isolated and pre-absorbed onto silica gel then purified by silica gel chromatography (EA/isohexanes) to afford 1.86 g (48%) tert-butyl 2-((4-hydroxybenzyl)amino)acetate INT-22 as a white powder. LCMS-ESI (m/z) calculated for C13H19NO3: 237 found 236 [M−H]−, tR=1.20 min (Method 10). 1H NMR (400 MHz, DMSO) δ 9.24 (s, 1H), 7.12-7.05 (m, 2H), 6.73-6.66 (m, 2H), 3.55 (s, 2H), 3.12 (s, 2H), 2.15 (s, 1H) 1.41 (s, 9H).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[C:8]([O:10][C:11]([F:14])([F:13])[F:12])[CH:7]=[CH:6][C:5]=1[S:15](Cl)(=[O:17])=[O:16])([O-:3])=[O:2].[N:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[N+:1]([C:4]1[CH:9]=[C:8]([O:10][C:11]([F:14])([F:13])[F:12])[CH:7]=[CH:6][C:5]=1[S:15]([NH:1][C:4]1[CH:5]=[CH:6][CH:7]=[C:23]2[C:24]=1[N:19]=[CH:20][CH:21]=[CH:22]2)(=[O:17])=[O:16])([O-:3])=[O:2]
Reactant: c1ccncc1
Reactant: O=[N+]([O-])c1cc(OC(F)(F)F)ccc1S(=O)(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: O=[N+]([O-])c1cc(OC(F)(F)F)ccc1S(=O)(=O)Nc1cccc2cccnc12
Yield: 35 %

Procedure:
In a similar fashion using route 14 general procedure 27, 8-aminoqunoline (500 mg, 3.47 mmol), 2-nitro-4-trifluoromethoxy-benzenesulfonyl chloride (Intermediate 221) (1.4 g, 4.51 mmol), pyridine (5 ml), DMAP (cat.) and DCM (3 ml) gave the title compound (500 mg, 35%) after purification by column chromatography with n-hexane/EtOAc (90:10) as the eluent.
Reaction SMILES: C[O:2][C:3](=[O:20])[CH:4]([OH:19])[C:5]1[CH:14]=[C:13]2[C:8]([CH2:9][CH2:10][C:11](=[O:16])[N:12]2[CH3:15])=[CH:7][C:6]=1[O:17][CH3:18].[Cr](O)(O)(=O)=O>CC(C)=O.S(=O)(=O)(O)O.O>[CH3:18][O:17][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][C:5]=1[C:4](=[O:19])[C:3]([OH:20])=[O:2])[N:12]([CH3:15])[C:11](=[O:16])[CH2:10][CH2:9]2
Reactant: COC(=O)C(O)c1cc2c(cc1OC)CCC(=O)N2C
Agent: O=[Cr](=O)(O)O
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CC(C)=O
Product: COc1cc2c(cc1C(=O)C(=O)O)N(C)C(=O)CC2
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 88.4 %

Procedure:
To a solution of 1.2 g (0.0043 m) of hydroxy-(6-methoxy-1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-7-yl) acetic acid methyl ester dissolved in 40 ml of acetone was added dropwise 1.6 ml of a 2.67 m solution of chromic acid in sulfuric acid/H2O (Jones reagent). The mixture was stirred for 90 minutes at room temperature. The acetone was decanted from the green precipitate and evaporated. The residue was dissolved in ethyl acetate and washed with saturated sodium bicarbonate. The ethyl acetate solution was dried with sodium sulfate and evaporated to yield 1.0 g (84%) of (6-methoxy-1-methyl-2-oxo-1,2,3,4-tetrahydro quinolin-7-yl)-oxo acetic acid as a yellow amorphous solid. 1H NMR (CDCl3) δ 2.60 (m, 2H), 2.90 (m, 2H), 3.20 (s, 3H), 3.80 (s, 3H), 3.90 (s, 3H), 6.80 (s, 1H), 7.40 (s, 1H). Mass spectrum: m/e=277.9 (p+1). TLC (3/1 chloroform/ethyl acetate) Rf=0.8.
Reaction SMILES: [CH3:1][C:2]([S:5]([NH2:7])=[O:6])([CH3:4])[CH3:3].[F:8][C:9]([F:24])([F:23])[CH2:10][O:11][C:12]1[CH:21]=[CH:20][CH:19]=[C:18]2[C:13]=1[CH2:14][CH2:15][CH2:16][C:17]2=O>C1COCC1.C(O[Ti](OCC)(OCC)OCC)C>[CH3:1][C:2]([S@:5](/[N:7]=[C:17]1/[CH2:16][CH2:15][CH2:14][C:13]2[C:18]/1=[CH:19][CH:20]=[CH:21][C:12]=2[O:11][CH2:10][C:9]([F:8])([F:23])[F:24])=[O:6])([CH3:4])[CH3:3]
Reactant: O=C1CCCc2c(OCC(F)(F)F)cccc21
Reactant: CC(C)(C)S(N)=O
Agent: CCO[Ti](OCC)(OCC)OCC
Solvent: C1CCOC1
Product: CC(C)(C)[S@@](=O)/N=C1/CCCc2c(OCC(F)(F)F)cccc21
Temperature: 75 °C

Procedure:
To a stirring solution of 2-methylpropane-2-sulfinamide (339 mg, 2.79 mmol) and 5-(2,2,2-trifluoroethoxy)-3,4-dihydronaphthalen-1(2H)-one (650 mg, 2.66 mmol) in THF (3 mL) was added tetraethoxytitanium (1.10 mL, 5.32 mmol) at rt. The reaction mixture was heated at 75° C. for 14 h. The reaction mixture was cooled to give Intermediate 13A which was used directly in the next step. LCMS=3.86 min [M+1]=347 (Method B).
Reaction SMILES: [C:1]([O:4][CH2:5][C:6]1[CH2:7][S:8][C@@H:9]2[CH:16]([NH:17][C:18](=[O:31])[C:19]([C:23]3[N:24]=[C:25]([NH:28][CH:29]=[O:30])[S:26][CH:27]=3)=[N:20][O:21][CH3:22])[C:15](=[O:32])[N:10]2[C:11]=1[C:12]([O-:14])=[O:13])(=O)C.[Na+].O.O.[Cl-].[Ca+2].[Cl-]>CO>[CH:29]([NH:28][C:25]1[S:26][CH:27]=[C:23]([C:19](=[N:20][O:21][CH3:22])[C:18]([NH:17][CH:16]2[C:15](=[O:32])[N:10]3[C:11]([C:12]([OH:14])=[O:13])=[C:6]([CH2:5][O:4][CH3:1])[CH2:7][S:8][C@H:9]23)=[O:31])[N:24]=1)=[O:30]
Reactant: CON=C(C(=O)NC1C(=O)N2C(C(=O)[O-])=C(COC(C)=O)CS[C@H]12)c1csc(NC=O)n1
Agent: [Ca+2]
Agent: [Cl-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: COCC1=C(C(=O)O)N2C(=O)C(NC(=O)C(=NOC)c3csc(NC=O)n3)[C@H]2SC1
Temperature: 70 °C
Reaction time: 0.58 h
Yield: 66.6 %

Procedure:
1 g of sodium 3-acetoxymethyl-7-[2-(2-formylaminothiazol-4-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylate were dissolved in 12 ml of 50% v/v aqueous methanol, and 20 g of calcium chloride dihydrate were added. The mixture was then stirred at 70° C. for 35 minutes, after which it was diluted with 30 ml of ice-water and insolubles were filtered off. The filtrate was acidified with hydrochloric acid and extracted three times, each time with 50 ml of ethyl acetate. The extracts were combined, washed with an aqueous solution of sodium chloride, dehydrated over anhydrous magnesium sulphate and concentrated by evaporation under reduced pressure. The residue was dissolved in ethyl acetate, and diethyl ether was added thereto. The resulting solid was separated, giving 0.6 g (yield 66.7%) of the title compound.
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]([CH3:24])=[C:5]([C:20]([O:22][CH3:23])=[O:21])[CH:6]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=2)[C:7]=1[C:8](O)=[O:9].[N:25]1[CH:30]=[CH:29][CH:28]=[C:27]([CH2:31][C:32]2[CH:37]=[CH:36][C:35](/[CH:38]=[CH:39]/[CH2:40][OH:41])=[CH:34][CH:33]=2)[CH:26]=1.C1(N=C=NC2CCCCC2)CCCCC1>C1(C)C=CC=CC=1>[CH3:24][C:4]1[NH:3][C:2]([CH3:1])=[C:7]([C:8]([O:41][CH2:40]/[CH:39]=[CH:38]/[C:35]2[CH:34]=[CH:33][C:32]([CH2:31][C:27]3[CH:26]=[N:25][CH:30]=[CH:29][CH:28]=3)=[CH:37][CH:36]=2)=[O:9])[CH:6]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=2)[C:5]=1[C:20]([O:22][CH3:23])=[O:21]
Reactant: OC/C=C/c1ccc(Cc2cccnc2)cc1
Reactant: COC(=O)C1=C(C)NC(C)=C(C(=O)O)C1c1cccc([N+](=O)[O-])c1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: Cc1ccccc1
Product: COC(=O)C1=C(C)NC(C)=C(C(=O)OC/C=C/c2ccc(Cc3cccnc3)cc2)C1c1cccc([N+](=O)[O-])c1
Temperature: 25 °C

Procedure:
332 mg (1 mM) of 1,4-dihydro-2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)pyridine-3-carboxylic acid together with 225 mg (1 mM) of (E)-3-{4-(3-pyridylmethyl)phenyl)-2-propen-1-ol, 248 mg (1.2 mM) of dicyclohexylcarbodiimide and 134 mg (1.1 mM) of 4-N,N-dimethylaminopyridine were dissolved in 5 ml of toluene, while heating, and refluxed for six hours. The solution was cooled to room temperature, and the crystals produced were filtered off. The filtrate was washed with water and dried over anhydrous sodium sulfate. After the solvent was distilled off, the residue was purified by chromatography on a silica gel column, whereby the captioned compound was obtained. The yield was 481 mg (89%).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:21]([C:22]([O:24]C)=[O:23])=[C:20]([C:26]([F:29])([F:28])[F:27])[CH:19]=[CH:18][N:17]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>CO>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([NH:15][C:16]2[C:21]([C:22]([OH:24])=[O:23])=[C:20]([C:26]([F:29])([F:27])[F:28])[CH:19]=[CH:18][N:17]=2)=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)c1c(C(F)(F)F)ccnc1Nc1ccc(OCc2ccccc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)c1c(C(F)(F)F)ccnc1Nc1ccc(OCc2ccccc2)cc1
Temperature: 60 °C
Reaction time: 3 h
Yield: 89.8 %

Procedure:
To a mixture of methyl 2-{[4-(benzyloxy)phenyl]amino}-4-(trifluoromethyl)pyridine-3-carboxylate (255 mg) in MeOH (5 mL) was added 1N NaOH (2.54 mL), and the mixture was stirred at 60° C. for 3 h. After MeOH was evaporated, to the water phase was added 1N HCl (pH=ca. 2). The precipitate was collected by filtration to give the title compound (221 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][CH:12]([CH2:27][OH:28])[C:13]([NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:17]=2)=[O:14])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[S:29](Cl)([CH3:32])(=[O:31])=[O:30]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([NH:11][CH:12]([CH2:27][O:28][S:29]([CH3:32])(=[O:31])=[O:30])[C:13]([NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:17]=2)=[O:14])(=[O:9])=[O:10])=[CH:6][CH:7]=1
Reactant: CS(=O)(=O)Cl
Reactant: CCOC(=O)c1cccc(NC(=O)C(CO)NS(=O)(=O)c2ccc(Cl)cc2)c1
Product: CCOC(=O)c1cccc(NC(=O)C(COS(C)(=O)=O)NS(=O)(=O)c2ccc(Cl)cc2)c1

Procedure:
The procedure described in Example 65 was repeated, except that (RS)-2-(4-chlorobenzenesulfonylamino)-N-(3-ethoxycarbonylphenyl)-3-hydroxypropanamide (1 g) was reacted with mesyl chloride to obtain (RS)-2-(4-chlorobenzenesulfonylamino)-N-(3-ethoxycarbonylphenyl)-3-methanesulfonyloxypropanamide (763 mg). Recrystallization from CHCl3 was carried out.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH2:33][C:34]1[CH:43]=[CH:42][C:37]2[O:38][CH2:39][CH2:40][O:41][C:36]=2[CH:35]=1)[CH:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][N:17]2[C:26]3[CH:25]=[C:24]([O:27][CH3:28])[CH:23]=[C:22]([C:29]([OH:31])=O)[C:21]=3[CH:20]=[CH:19][C:18]2=[O:32])[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.CN.F[P-](F)(F)(F)(F)F.[N:54]1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)[C:58]2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O.O>[O:38]1[C:37]2[CH:42]=[CH:43][C:34]([CH2:33][N:8]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][N:17]4[C:26]5[C:21](=[C:22]([C:29]([NH:54][CH3:58])=[O:31])[CH:23]=[C:24]([O:27][CH3:28])[CH:25]=5)[CH:20]=[CH:19][C:18]4=[O:32])[CH2:11][CH2:10]3)[C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:35][C:36]=2[O:41][CH2:40][CH2:39]1
Reactant: COc1cc(C(=O)O)c2ccc(=O)n(CCN3CCC(N(Cc4ccc5c(c4)OCCO5)C(=O)OC(C)(C)C)CC3)c2c1
Reactant: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Agent: CN
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: CNC(=O)c1cc(OC)cc2c1ccc(=O)n2CCN1CCC(N(Cc2ccc3c(c2)OCCO3)C(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 84.7 %

Procedure:
463 mg of 1-(2-(4-((tert-butoxycarbonyl) (2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino)piperidin-1-yl)ethyl)-7-methoxy-2-oxo-1,2-dihydroquinoline-5-carboxylic acid and 144 mg of methylamine hydrochloride were dissolved in 10 mL of N,N-dimethylformamide. To the mixture, 706 mg of (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate and 0.47 mL of N,N-diisopropylethylamine were added and stirred at room temperature overnight. The reaction mixture was poured into water, and extracted with a mixture of ethyl acetate: toluene=5:1. The organic layer was washed sequentially with water and aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [Silica Gel; Kanto Chemical Co., Inc., Silica Gel 60, eluent; chloroform:methanol=20:1], to give 401 mg of tert-butyl (2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(1-(2-(7-methoxy-5-((methylamino)carbonyl)-2-oxoquinolin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate as a pale brown foam.
Reaction SMILES: C([O:4][C@@H:5]1[C@@H:32]([O:33]C(=O)C)[C@H:31]([O:37][C@@H:38]2[O:75][C@H:74]([CH2:76][O:77]C(=O)C)[C@H:49]([O:50][C@H:51]3[O:68][C@H:67]([CH2:69][O:70]C(=O)C)[C@H:62]([O:63]C(=O)C)[C@H:57]([O:58]C(=O)C)[C@H:52]3[O:53]C(=O)C)[C@H:44]([O:45]C(=O)C)[C@H:39]2[O:40]C(=O)C)[C@@H:30]([CH2:81][O:82]C(=O)C)[O:29][C@H:6]1[O:7][CH2:8][CH2:9][S:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])(=O)C>C[O-].[Na+]>[C@H:51]1([O:50][C@H:49]2[C@@H:74]([CH2:76][OH:77])[O:75][C@@H:38]([O:37][C@@H:31]3[C@@H:30]([CH2:81][OH:82])[O:29][C@@H:6]([O:7][CH2:8][CH2:9][S:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[C@H:5]([OH:4])[C@H:32]3[OH:33])[C@H:39]([OH:40])[C@H:44]2[OH:45])[O:68][C@H:67]([CH2:69][OH:70])[C@H:62]([OH:63])[C@H:57]([OH:58])[C@H:52]1[OH:53]
Reactant: CCCCCCCCCCCCCCCCCCSCCO[C@@H]1O[C@H](COC(C)=O)[C@@H](O[C@@H]2O[C@H](COC(C)=O)[C@H](O[C@H]3O[C@H](COC(C)=O)[C@H](OC(C)=O)[C@H](OC(C)=O)[C@H]3OC(C)=O)[C@H](OC(C)=O)[C@H]2OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O
Agent: C[O-]
Agent: [Na+]
Product: CCCCCCCCCCCCCCCCCCSCCO[C@@H]1O[C@H](CO)[C@@H](O[C@@H]2O[C@H](CO)[C@H](O[C@H]3O[C@H](CO)[C@H](O)[C@H](O)[C@H]3O)[C@H](O)[C@H]2O)[C@H](O)[C@H]1O
Yield: 87.6 %

Procedure:
A solution of 65 (1.0 g, 0.81 mmol) in methanolic sodium methoxide (0.003M, 100 ml) was left at room temperature for 24 h and neutralized with Duolite C26 (H+) resin. The solvent was removed and the residue was dissolved in water (300 ml) and lyophilized to give 66 (580 mg, 88%) with [α]D21 +42° (c 0.7, dimethylsulfoxide). 1H-NMR (DMSO-d6, 50°, D2O added, Me4Si) δ 4.81 (d, 1H, J=3.5 Hz, H1"), 4.27, 4.24 (2d, each 1H, J=7 and 8 Hz, H1 and H1'), 2.67, 2.52 (2t, each 2H, J=7.5 Hz, CH2 --S--CH2), 0.86 (t, 3H, J=6.5 Hz, Me). 13C-NMR (CDCl3 --CD3OD 1:5) δ 105.2, 104.1 (2d, J=162 Hz, Cl, Cl'), 102.6 (d, J=172 Hz, Cl"), 81.1, 80.0, 76.3 (3C), 74.6, (2C), 72.9, 72.5, 71.1, 70.9, 70.4, 70.3 (CH2), 62.7 (CH2), 62.0 (CH2), 61.3 (CH2), 33.2-29.7 (CH2), 23.5 (CH2), 14.4 (CH3).