Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [K+].[Br-].[CH3:3][C:4]1[S:8][CH:7]=[C:6](/[CH:9]=[C:10](/[C@H:12]2[O:30][C:28](=[O:29])[CH2:27][C@H:26]([OH:31])[C@@H:25]([CH3:32])[C:23](=[O:24])[C@H:22]([CH3:33])[C@@H:21]([OH:34])[C@@H:20]([CH3:35])[CH2:19][CH2:18][CH2:17][C@H:15]3O[C@H:14]3[CH2:13]2)\[CH3:11])[N:5]=1.CC1SC=C(/C=C(/[C@H]2OC(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC[C@H]3O[C@H]3C2)\CO)N=1.CC1SC=C(/C=C/[C@H]2OC(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC[C@H]3O[C@H]3C2)N=1>CO>[CH3:3][C:4]1[S:8][CH:7]=[C:6](/[CH:9]=[C:10](/[C@H:12]2[O:30][C:28](=[O:29])[CH2:27][C@H:26]([OH:31])[C@@H:25]([CH3:32])[C:23](=[O:24])[C@H:22]([CH3:33])[C@@H:21]([OH:34])[C@@H:20]([CH3:35])[CH2:19][CH2:18][CH2:17][CH:15]=[CH:14][CH2:13]2)\[CH3:11])[N:5]=1
Reactant: C/C(=C\c1csc(C)n1)[C@@H]1C[C@@H]2O[C@@H]2CCC[C@H](C)[C@H](O)[C@@H](C)C(=O)[C@H](C)[C@@H](O)CC(=O)O1
Agent: C/C(=C\c1csc(C)n1)[C@@H]1C/C=C\CCC[C@H](C)[C@H](O)[C@@H](C)C(=O)[C@H](C)[C@@H](O)CC(=O)O1
Agent: Cc1nc(/C=C(\CO)[C@@H]2C[C@@H]3O[C@@H]3CCC[C@H](C)[C@H](O)[C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O2)cs1
Agent: Cc1nc(/C=C/[C@@H]2C[C@@H]3O[C@@H]3CCC[C@H](C)[C@H](O)[C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O2)cs1
Solvent: CO
Product: C/C(=C\c1csc(C)n1)[C@@H]1CC=CCCC[C@H](C)[C@H](O)[C@@H](C)C(=O)[C@H](C)[C@@H](O)CC(=O)O1

Procedure:
colorless amorphous solid; [α]22D −114.0 (c 10.0, MeOH); UV (MeOH) λmax nm (ε) 211 (16500), 248 (12500); IR (KBr) νmax 3440, 2933, 2877, 2858, 1730, 1708, 1457, 1244, 981 cm−1; 1H NMR (CDCl3, 300 MHz) δ 6.96 (1H, s, H-19), 6.56 (1H, bs, H-17), 5.47 (1H, dd, J=9.2, 3.0 Hz, H-15), 5.43 (1H, m, H-12), 5.40 (1H, m, H-13), 4.40 (1H, ddd, J=6.2, 6.1, 6.1 Hz, H-3), 3.69 (1H, dd, J=5.7, 3.6 Hz, H-7), 3.01 (1H, dq, J=5.7, 6.9 Hz, H-6), 3.01 (1H, bs, 3-OH), 2.84 (1H, dq, J=5.2, 7.0 Hz, H-4), 2.68 (3H, s, H-21), 2.66 (1H, ddd, 1=16.4, 9.2, 7.3 Hz, H-14a), 2.64 (1H, dd, J=15.9, 7.1 Hz, H-2a), 2.54 (1H, dd, J=15.9, 6.1 Hz, H-2b), 2.38 (1H, bd, J=16.4 Hz, H-14b), 2.35 (1H, bs, 7-OH), 2.07 (3H, bs, H-27), 2.03 (2H, m, H-11), 1.62 (1H, m, H-10a), 1.53 (1H, m, H-8), 1.35 (1H, m, H-9a), 1.22 (1H, M, H-9b), 1.19 (3H, d, J=6.9 Hz, H-24),1.14 (3H, d, J=6.9 Hz, H-23), 1.10 (1H, m, H-10b), 0.95 (3H, d, J=6.9 Hz, H-25); 13C NMR, see Table 1; EIMS m/z 463 [M]+ (5), 324 (8), 290 (8), 204 (7), 168 (100), 164 (15), 139 (36); HREIMS m/z 463.2381 (calcd. for C23H37NO5S, 463.2392).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6](B(O)O)[CH:5]=[CH:4][N:3]=1.Cl[C:12]1[N:17]=[CH:16][C:15]([CH2:18][NH2:19])=[CH:14][CH:13]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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>[CH3:1][C:2]1[CH:7]=[C:6]([C:12]2[CH:13]=[CH:14][C:15]([CH2:18][NH2:19])=[CH:16][N:17]=2)[CH:5]=[CH:4][N:3]=1
Reactant: NCc1ccc(Cl)nc1
Reactant: Cc1cc(B(O)O)ccn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Product: Cc1cc(-c2ccc(CN)cn2)ccn1
Temperature: 96 °C
Reaction time: 8 h

Procedure:
A mixture of (2-methylpyridin-4-yl)boronic acid 15-1 (476 mg, 3.48 mmol), (6-chloropyridin-3-yl)methanamine 18-1 (496 mg, 3.48 mmol), Pd(PPh3)4 (202 mg, 0.175 mmol) and K3PO4 (1113 mg, 5.25 mmol) in dioxane (5 mL) was stirred at 96° C. under argon overnight. After cooling to room temperature, the mixture was filtered through celite and washed with ethyl acetate. The filtrate was concentrated by rotavap and the residue subjected to silica gel column chromatography with 7% ammonia-saturated methanol in dichloromethane as eluent to give (2′-methyl-[2,4′-bipyridin]-5-yl)methanamine 18-2 as an oil.
Reaction SMILES: CN(C)C=O.[S:6]([Cl:10])(Cl)(=[O:8])=[O:7].[CH3:11][O:12][C:13]1[CH:14]=[C:15]([CH:26]=[C:27]([O:31][CH3:32])[C:28]=1[O:29][CH3:30])[CH2:16][C:17]1[S:21][C:20]2[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=2[CH:18]=1>>[CH3:11][O:12][C:13]1[CH:14]=[C:15]([CH:26]=[C:27]([O:31][CH3:32])[C:28]=1[O:29][CH3:30])[CH2:16][C:17]1[S:21][C:20]2[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=2[C:18]=1[S:6]([Cl:10])(=[O:8])=[O:7]
Reactant: COc1cc(Cc2cc3ccccc3s2)cc(OC)c1OC
Reactant: O=S(=O)(Cl)Cl
Solvent: CN(C)C=O
Product: COc1cc(Cc2sc3ccccc3c2S(=O)(=O)Cl)cc(OC)c1OC

Procedure:
2-(3,4,5-trimethoxybenzyl)-benzo[b]thiophene-3-sulfonylchloride was prepared in the same manner as described in Example 40B. Reaction of dimethylformamide (DMF; 4.8 mmoles, 0.40 mls), sulfuryl chloride (4.1 mmoles, 0.33 mls) and 2-(3,4,5-trimethoxybenzyl)-benzo[b]thiophene (2.4 mmoles, 0.75 g) yielded, after flash chromatography using 20% ethyl acetate/hexanes, 0.29 g (30%) of a yellow-orange oil.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([O:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([OH:28])=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][CH:17]=2)[C:5]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)=[N:6][C:7]=1[CH3:8].C(=O)([O-])[O-].[K+].[K+].Br[CH2:36][CH2:37][CH2:38][OH:39]>CN(C)C=O>[CH3:1][C:2]1[CH:3]=[C:4]([O:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:28][CH2:36][CH2:37][CH2:38][OH:39])=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][CH:17]=2)[C:5]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)=[N:6][C:7]=1[CH3:8]
Reactant: COc1cc2c(Oc3cc(C)c(C)nc3-c3cccnc3)ccnc2cc1O
Reactant: OCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1cc2c(Oc3cc(C)c(C)nc3-c3cccnc3)ccnc2cc1OCCCO
Temperature: 25 °C
Reaction time: 8 h
Yield: 24 %

Procedure:
4-(5,6-Dimethyl-[2,3′]bipyridin-3-yloxy)-6-methoxy-quinolin-7-ol (compound 345) (45 mg) was dissolved in N,N-dimethylformamide (2 ml) to prepare a solution, potassium carbonate (50 mg) and 3-bromo-1-propanol (0.03 ml) were added to the solution, and the mixture was stirred at room temperature overnight. The solvent was removed by distillation under the reduced pressure, water was then added to the residue, and the mixture was extracted with chloroform. The chloroform layer was washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography using chloroform-acetone to give the title compound (13 mg, yield 24%).
Reaction SMILES: [C:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:19]([C:20]3[S:24][C:23]4[CH:25]=[CH:26][CH:27]=[CH:28][C:22]=4[CH:21]=3)=[CH:18][C:17](=[O:29])[C:13]([C:14]([OH:16])=[O:15])=[CH:12]2)=[CH:7][CH:6]=1)(=[O:3])[CH3:2].C(N(CC)CC)C.C(Cl)(=O)OCC.[CH2:43]1[C:51]2[C:46](=[CH:47][C:48](O)=[CH:49][CH:50]=2)[CH2:45][CH2:44]1>C(Cl)Cl>[C:1]([O:4][C:5]1[CH:6]=[CH:7][C:8]([N:11]2[C:19]([C:20]3[S:24][C:23]4[CH:25]=[CH:26][CH:27]=[CH:28][C:22]=4[CH:21]=3)=[CH:18][C:17](=[O:29])[C:13]([C:14]([O:16][CH:43]3[C:51]4[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=4)[CH2:45][CH2:44]3)=[O:15])=[CH:12]2)=[CH:9][CH:10]=1)(=[O:3])[CH3:2]
Reactant: Oc1ccc2c(c1)CCC2
Reactant: CC(=O)Oc1ccc(-n2cc(C(=O)O)c(=O)cc2-c2cc3ccccc3s2)cc1
Agent: CCOC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)Oc1ccc(-n2cc(C(=O)OC3CCc4ccccc43)c(=O)cc2-c2cc3ccccc3s2)cc1
Temperature: -40 °C
Yield: 54 %

Procedure:
In 18 ml of anhydrous methylene chloride was dissolved 0.36 g of 1-(4-acetoxyphenyl)-6-(2-benzo[b]thienyl)-4-oxo-1,4-dihydronicotinic acid, and to this solution was added 0.137 ml of triethylamine at room temperature. The reaction mixture thus obtained was cooled to -40° C., and 0.094 ml of ethyl chlorocarbonate was added thereto. The resulting mixture was subjected to reaction at the same temperature for 1 hour. This reaction mixture was then mixed with 0.14 g of 5-indanol. The mixture was subjected to reaction for 1 hour, and elevated to room temperature. After completion of the reaction, the reaction mixture was washed successively with 15 ml of water and a saturated aqueous solution of sodium chloride, and then dried with anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and the residue was purified by a column chromatography (Wako Silica Gel C-200; eluent: chloroform) to obtain 0.25 g of indanyl 1-(4-acetoxyphenyl)-6-(2-benzo[b]thienyl)-4 -oxo-1,4-dihydronicotinate having a melting point of 234°-236° C.
Reaction SMILES: [N+]([O-])(O)=O.[F:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13]([NH2:15])=[NH:14])=[CH:8][CH:7]=1.[OH-].[Na+].CO[CH2:20][CH2:21]O>>[CH3:10][C:9]1[NH:12][CH:13]=[C:20]([CH3:21])[C:8]=1[C:7]1[CH:6]=[CH:11][N:15]=[C:13]([NH:12][C:9]2[CH:8]=[CH:7][C:6]([F:5])=[CH:11][CH:10]=2)[N:14]=1
Reactant: N=C(N)Nc1ccc(F)cc1
Reactant: COCCO
Agent: [Na+]
Agent: [OH-]
Solvent: O=[N+]([O-])O
Product: Cc1c[nH]c(C)c1-c1ccnc(Nc2ccc(F)cc2)n1
Yield: 62 %

Procedure:
To a mixture of 3-dimethylamino-1-(2,4-dimethyl-1H-pyrrol-3-yl)-propenone (1 mmol, 0.19 g) and 4-fluorophenyl guanidine nitrate (2 mmol, 0.44 g) in 2-methoxyethanol (5 mL) was added NaOH (40 mg). The reaction mixture was heated at 100–120° C. under N2 for 6 h. The solvent was evaporated to dryness and the residue was purified by flash chromatography (1:2 EtOAc/PE). Recrystallisation from EtOAc/PE afforded the title compound (174 mg, 62%) as brown crystals. 1H-NMR (CDCl3) δ: 2.21 (s, 3H, CH3), 2.43 (s, 3H, CH3), 6.33 (s, 1H, pyrrolyl-H), 6.73 (d, 1H, J=5.3 Hz, pyrimidinyl-H), 7.00 (m, 2H, Ph-H), 7.79 (m, 2H, Ph-H), 8.28 (d, 1H, J=5.3 Hz, pyrimidinyl-H), 9.16 (s, 1H, NH), 10.59 (s, 1H, NH).
Reaction SMILES: C([O:3][C:4]([C@H:6]([OH:34])[C@H:7]([NH:19][C:20]([CH2:22][CH2:23][CH2:24][C:25]1[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=1[C:27]([OH:29])=[O:28])=[O:21])[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:15]([F:18])([F:17])[F:16])=[O:5])C.C1COCC1.[OH-].[Na+]>CC(O)=O>[C:4]([C@H:6]([OH:34])[C@H:7]([NH:19][C:20]([CH2:22][CH2:23][CH2:24][C:25]1[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=1[C:27]([OH:29])=[O:28])=[O:21])[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:15]([F:18])([F:17])[F:16])([OH:5])=[O:3]
Reactant: CCOC(=O)[C@H](O)[C@@H](Cc1ccccc1C(F)(F)F)NC(=O)CCCc1ccccc1C(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: O=C(CCCc1ccccc1C(=O)O)N[C@H](Cc1ccccc1C(F)(F)F)[C@@H](O)C(=O)O
Reaction time: 4 h
Yield: 100 %

Procedure:
2-{3-[(1R,2R)-2-Ethoxycarbonyl-2-hydroxy-1-(2-trifluoromethyl-benzyl)-ethylcarbamoyl]-propyl}-benzoic acid was combined with THF (5 mL) and 10 M aqueous NaOH (96 μL, 4.0 eq.). The reaction was stirred for 4 hours. Upon completion of the reaction was completed, AcOH (1.5 mL) was added and the product was purified by preparative HPLC to yield the title compound (10 mg, 100% purity). MS m/z [M+H]+ calc'd for C22H22F3NO6, 454.14. found 454.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]2[CH2:18][CH2:19][O:20][C:21]3[CH:27]=[CH:26][C:25]([C:28]4[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=4)=[CH:24][C:22]=3[CH:23]=2)=[O:16])=[CH:10][CH:9]=1.ClC1C=CC=C(C(OO)=[O:43])C=1.S([O-])([O-])(=O)=S.[Na+].[Na+]>O1CCCC1>[O-:43][N+:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]2[CH2:18][CH2:19][O:20][C:21]3[CH:27]=[CH:26][C:25]([C:28]4[CH:29]=[CH:30][C:31]([CH3:34])=[CH:32][CH:33]=4)=[CH:24][C:22]=3[CH:23]=2)=[O:16])=[CH:10][CH:9]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: Cc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(Cc4ccccn4)cc2)CCO3)cc1
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(Cc4cccc[n+]4[O-])cc2)CCO3)cc1
Temperature: 25 °C
Reaction time: 17 h
Yield: 59.9 %

Procedure:
To a solution of N-[4—(2-pyridylmethyl)phenyl]-7—(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (200 mg) in tetrahydrofuran (10 ml) was added 3-chloro-perbenzoic acid (70%, 0.18 g) at 0° C., and the mixture was stirred at room temperature for 17 hours. To the reaction mixture was added sodium thio-sulfate solution, and the mixture was stirred for a few minutes. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution and saturated sodium chloride solution, dried with magnesium sulfate and concentrated to give crystals, which were collected by filtration and was recrystallized from ethanol to give N-[4—(1-oxidopyridin-2-ylmethyl)phenyl]-7—(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (Compound 162) (124 mg) as colorless crystals.
Reaction SMILES: C[O:2][C:3]([C:5]1[S:6][C:7]([C:11](=[O:22])[NH:12][CH:13]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([OH:21])[CH:16]=2)[CH3:14])=[CH:8][C:9]=1[CH3:10])=[O:4].O[Li].O>C1COCC1.O>[OH:21][C:17]1[CH:16]=[C:15]([CH:13]([NH:12][C:11]([C:7]2[S:6][C:5]([C:3]([OH:4])=[O:2])=[C:9]([CH3:10])[CH:8]=2)=[O:22])[CH3:14])[CH:20]=[CH:19][CH:18]=1
Reactant: COC(=O)c1sc(C(=O)NC(C)c2cccc(O)c2)cc1C
Agent: [Li]O
Solvent: C1CCOC1
Solvent: O
Product: Cc1cc(C(=O)NC(C)c2cccc(O)c2)sc1C(=O)O
Yield: 96.5 %

Procedure:
A solution of 5-[1-(3-hydroxy-phenyl)-ethyl-carbamoyl]-3-methyl-thiophene-2-carboxylic acid methyl ester (121 mg, 0.38 mmol) in THF/water (3 ml/1 ml) was treated with LiOH.H2O (158 mg, 3.8 mmol) at rt overnight. The reaction mixture was quenched with 1N HCl and extracted with EtOAc. The layers were separated. The organic layer was washed with brine, then dried over Na2SO4 and concentrated under reduced pressure to afford the desired product (112 mg, 100% yield).
Reaction SMILES: [C:1](=O)([O-])[O-:2].[Na+].[Na+].[F:7][CH2:8][CH2:9][NH:10][C:11](=[O:14])[O:12][CH3:13]>C1(C)C=CC(S([O-])(=O)=O)=CC=1.C([N+](CC)(CC)CC)C.CO>[F:7][CH2:8][CH:9]([NH:10][C:11](=[O:14])[O:12][CH3:13])[O:2][CH3:1]
Reactant: O=C([O-])[O-]
Reactant: COC(=O)NCCF
Agent: CC[N+](CC)(CC)CC
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: [Na+]
Solvent: CO
Product: COC(=O)NC(CF)OC
Reaction time: 1 h
Yield: 251.4 %

Procedure:
An undivided electrochemical flow cell was constructed from two 150 cm2 graphite block electrodes separated with a 6 mm Viton® gasket and plumbed to a 500 ml jar reservoir, a Teflon® lined pump and a refrigerated cooling system so that the contents of the reservoir could be continuously recirculated thorugh the cell and cooling system. The electrodes were connected to a power source and a voltage meter. The system was flushed with chromatography grade methanol to remove any contaminants. The reservoir was charged with 10-20 g of molecular sieves to keep the system dry, 290 g of chromatography grade methanol, 12 g (0.039 mol) of tetraethylammonium p-toluenesulfonate, 2 g (0.02 mol) of sodium carbonate, and 27.5 g of 91 percent purity (0.227 mol) of methyl 2-fluoroethylcarbamate and the resulting solution was circulated through the electrochemical cell while maintaining the current at 10 amperes and the temperature at 12°-16° C. After 1 hour gas chromatographic analysis indicated about 2 percent conversion. The current was increased to 12 amperes and the conversion went up to about 8 percent during the next hour and 39 percent after 6 hours. The process was continued overnight to increase the conversion to about 95 percent based on starting material and 81 percent based on product. The volatiles were removed under reduced pressure and the residue was dissolved in 200 ml of methylene chloride. The resulting solution was extracted with 100 ml of water, 100 ml of saturated aqueous sodium bicarbonate, and 100 ml of saturated aqueous sodium chloride and dried over magnesium sulfate. Evaporation of the volatiles under reduced pressure left 22.0 g of an oily residue which was found to be the title compound of about 81 percent purity by gas chromatography. The aqueous extracts were combined and extracted with methylene chloride to obtain another 7.6 g of the title compound of about 85 percent purity. The total yield recovered was about 85 percent of theory.
Reaction SMILES: [C:1]([NH:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([CH3:18])([CH3:17])[C:13]([O:15]C)=[O:14])=[CH:8][CH:7]=1)(=[O:3])[CH3:2].[OH-].[Na+]>C(O)C.O>[C:1]([NH:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([CH3:18])([CH3:17])[C:13]([OH:15])=[O:14])=[CH:8][CH:7]=1)(=[O:3])[CH3:2]
Reactant: COC(=O)C(C)(C)c1ccc(CNC(C)=O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CC(=O)NCc1ccc(C(C)(C)C(=O)O)cc1
Temperature: 70 °C
Reaction time: 1 h
Yield: 63.2 %

Procedure:
To a solution of methyl 2-(4-acetylaminomethylphenyl)-2-methylpropionate (23.47 g) in ethanol (160 ml) was added a solution of sodium hydroxide (7.53 g) in water (94 ml) and the mixture was stirred at 70° C. for 1 hr. The solvent was evaporated, and conc. hydrochloric acid was added. The resulting crystals were collected by filtration to give the title compound (14.0 g) as pale-yellow crystals, m.p.=166-169° C.
Reaction SMILES: [CH3:1][N:2]([CH3:29])[C:3]([N:5]1[CH:10]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=2)[C:9]([C:20]([O:22][CH:23]([CH3:25])[CH3:24])=[O:21])=[C:8]([CH3:26])[N:7]=[C:6]1[O:27]C)=[O:4].Cl>O1CCCC1.CO>[CH3:29][N:2]([CH3:1])[C:3]([N:5]1[CH:10]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=2)[C:9]([C:20]([O:22][CH:23]([CH3:24])[CH3:25])=[O:21])=[C:8]([CH3:26])[NH:7][C:6]1=[O:27])=[O:4]
Reactant: COC1=NC(C)=C(C(=O)OC(C)C)C(c2cccc([N+](=O)[O-])c2)N1C(=O)N(C)C
Agent: Cl
Solvent: C1CCOC1
Solvent: CO
Product: CC1=C(C(=O)OC(C)C)C(c2cccc([N+](=O)[O-])c2)N(C(=O)N(C)C)C(=O)N1
Temperature: 25 °C
Reaction time: 1 h
Yield: 70.7 %

Procedure:
A solution of crude 1-[(dimethylamino)carbonyl]-1,6-dihydro-2-methoxy-4-methyl-6-(3-nitrophenyl)-5-pyrimidinecarboxylic acid, 1-methylethyl ester (2.27 g), in tetrahydrofuran/methanol (20 ml each) was treated with 5N hydrochloric acid (3.0 ml, pH1) and stirred at room temperature for 1.0 hour. The reaction was then evaporated and partitioned between ethyl acetate and water. The organic phase was washed with saturated sodium chloride, dried (magnesium sulfate), and evaporated. The residue was crystallized from dichloromethane/isopropyl ether to give the title compound as colorless crystals (1.55 g), melting point 165°-166° C.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([N:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][N:18]=3)[CH:13]=[C:12]([CH2:20][CH2:21][CH:22]([OH:29])[C:23]3[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=3)[C:11]2=[O:30])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[C:31](OC(=O)C)(=[O:33])[CH3:32]>N1C=CC=CC=1>[N+:1]([C:4]1[CH:5]=[C:6]([N:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][N:18]=3)[CH:13]=[C:12]([CH2:20][CH2:21][CH:22]([O:29][C:31](=[O:33])[CH3:32])[C:23]3[CH:24]=[CH:25][N:26]=[CH:27][CH:28]=3)[C:11]2=[O:30])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: O=c1c(CCC(O)c2ccncc2)cc2cccnc2n1-c1cccc([N+](=O)[O-])c1
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)OC(CCc1cc2cccnc2n(-c2cccc([N+](=O)[O-])c2)c1=O)c1ccncc1
Temperature: 100 °C
Yield: 100 %

Procedure:
A mixture of 1-(3-nitrophenyl)-3-[3-hydroxy-3-(pyridin-4-yl)propyl]-1,8-naphthyridin-2(1H)-one (50 mg, 0.12 mmol; prepared in Example 20) in acetic anhydride (0.2 ml) and pyridine (0.3 ml) was heated at 100° C. for 20 min, concentrated, and extracted with chloroform. The extract was treated according to conventional techniques, concentrated, and then purified by flash column chromatography to afford 1-(3-nitrophenyl)-3-[3-acetyloxy-3-(pyridin-4-yl)propyl]-1,8-naphthyridin-2(1H)-one (55.2 mg, 100%; mp 69–71° C.).
Reaction SMILES: [N:1]#[N:2].[S:3]([NH:19][C@H:20]([C:28]([OH:30])=[O:29])[CH2:21][CH2:22][CH2:23][NH:24][C:25](=[NH:27])[NH2:26])([C:6]1[C:18]2[CH:17]=[CH:16][CH:15]=[C:11]([N:12]([CH3:14])[CH3:13])[C:10]=2[CH:9]=[CH:8][CH:7]=1)(=[O:5])=[O:4].O.[C:32]1([CH3:42])[CH:37]=[CH:36][C:35]([S:38]([OH:41])(=[O:40])=[O:39])=[CH:34][CH:33]=1.[CH:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>C(O)CCCCC>[N:1]#[N:2].[C:32]1([CH3:42])[CH:33]=[CH:34][C:35]([S:38]([OH:41])(=[O:39])=[O:40])=[CH:36][CH:37]=1.[C:32]1([CH3:42])[CH:33]=[CH:34][C:35]([S:38]([OH:41])(=[O:39])=[O:40])=[CH:36][CH:37]=1.[CH2:47]([O:29][C:28](=[O:30])[C@H:20]([CH2:21][CH2:22][CH2:23][NH:24][C:25](=[NH:26])[NH2:27])[NH:19][S:3]([C:6]1[C:18]2[CH:17]=[CH:16][CH:15]=[C:11]([N:12]([CH3:13])[CH3:14])[C:10]=2[CH:9]=[CH:8][CH:7]=1)(=[O:4])=[O:5])[CH2:48][CH2:43][CH2:44][CH2:45][CH3:46]
Reactant: CN(C)c1cccc2c(S(=O)(=O)N[C@@H](CCCNC(=N)N)C(=O)O)cccc12
Reactant: c1ccccc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: N#N
Solvent: CCCCCCO
Solvent: O
Product: CCCCCCOC(=O)[C@H](CCCNC(=N)N)NS(=O)(=O)c1cccc2c(N(C)C)cccc12
Temperature: 100 °C
Yield: 95 %

Procedure:
A mixture of 1.0 gram of N2 -dansyl-L-arginine and 1.4 gram of p-toluenesulfonic acid monohydrate in 10 ml of n-hexyl alcohol was heated for 30 minutes at 100°C. To the thus obtained clear solution, 100 ml of benzene was added, and the mixture was refluxed for 3 hours, removing water by azeotropic distillation. After the solvent was removed by distillation, 50 ml of ethyl ether and 50 ml of petroleum ether were added to the residue to give a crystalline mass. Crystallization from acetone gave N2 -dansyl-L-arginine n-hexyl ester di(p-toluenesulfonate) in 95% yield; mp. 190°-193°C.
Reaction SMILES: C[C:2]([CH3:5])([O-:4])[CH3:3].[Na+].O1CCCC1.[I-].C[S+](C)C.OC(C1[C:24]([O:29][CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH2:38][C:39]3[N:40]=[C:41]([C:45]4[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=4)[O:42][C:43]=3[CH3:44])=[CH:33][CH:32]=2)=[N:25][CH:26]=[CH:27][CH:28]=1)S([O-])(=O)=O.[Na+]>CS(C)=O.O>[CH3:44][C:43]1[O:42][C:41]([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)=[N:40][C:39]=1[CH2:38][O:37][C:34]1[CH:33]=[CH:32][C:31]([CH2:30][O:29][C:24]2[C:3]([CH:2]3[CH2:5][O:4]3)=[CH:28][CH:27]=[CH:26][N:25]=2)=[CH:36][CH:35]=1
Reactant: Cc1oc(-c2ccccc2)nc1COc1ccc(COc2ncccc2C(O)S(=O)(=O)[O-])cc1
Reactant: CC(C)(C)[O-]
Agent: C[S+](C)C
Agent: [I-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: C1CCOC1
Solvent: O
Product: Cc1oc(-c2ccccc2)nc1COc1ccc(COc2ncccc2C2CO2)cc1
Temperature: 25 °C
Reaction time: 0.83 h

Procedure:
Sodium t-butoxide (2.86 g) was added to dimethyl sulfoxide (20 ml), and after stirring at room temperature for 50 min., tetrahydrofuran (30 ml) was added and ice-cooled. Trimethylsulfonium iodide (4.04 g) was added to the mixture, and after stirring under ice-cooling for 10 min., a solution of sodium hydroxy[2-({4-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]benzyl}oxy)pyridin-3-yl]methanesulfonate (5 g) in dimethyl sulfoxide (15 ml) was dropwise added under ice-cooling and the mixture was stirred under ice-cooling for 1 hr. and at room temperature for 1 hr. The reaction solution was poured into iced water (100 ml) and extracted twice with t-butylmethyl ether (50 ml). The organic layers were combined, washed 4 times with water (50 ml) and concentrated under reduced pressure to give 2-({4-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]benzyl}oxy)-3-oxiran-2-ylpyridine.
Reaction SMILES: [C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]([O:11][C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH2:18][CH:17]([CH2:22][OH:23])[CH2:16][CH2:15]3)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].C(Cl)Cl.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>>[C:1]([C@H:5]1[CH2:6][CH2:7][C@H:8]([O:11][C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH2:18][CH:17]([CH:22]=[O:23])[CH2:16][CH2:15]3)[CH2:9][CH2:10]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)[C@H]1CC[C@H](Oc2ccc3c(c2)CCC(CO)C3)CC1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: CC(C)(C)[C@H]1CC[C@H](Oc2ccc3c(c2)CCC(C=O)C3)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of [6-(trans-4-tert-butyl-cyclohexyloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]-methanol (73 mg, 0.23 mmol) in methylene chloride (1.478 mL, 23.07 mmol) was added Dess-Martin periodinane (0.1468 g, 0.3460 mmol) and was stirred at room temperature for 1 hour. After being passed through silica gel plug, the solvent was concentrated down to give product (27 mg, 37%). LCMS: Rf=2.39 min, m/z=315.00.
Reaction SMILES: [CH:1]12[CH2:9][CH:5]3[CH2:6][CH:7]([CH2:8]1)[C:3]([NH:10][C:11]([NH2:13])=[S:12])([CH2:4]3)[CH2:2]2.Br[CH:15]([CH:21]([CH3:23])[CH3:22])[C:16](OCC)=[O:17]>>[CH:21]([CH:15]1[S:12][C:11]([NH:10][C:3]23[CH2:4][CH:5]4[CH2:9][CH:1]([CH2:8][CH:7]2[CH2:6]4)[CH2:2]3)=[N:13][C:16]1=[O:17])([CH3:23])[CH3:22]
Reactant: CCOC(=O)C(Br)C(C)C
Reactant: NC(=S)NC12CC3CC(CC1C3)C2
Product: CC(C)C1SC(NC23CC4CC(CC2C4)C3)=NC1=O

Procedure:
Synthesis was performed from N-tricyclo[3.3.1.0˜3,7˜]non-3-ylthiourea and ethyl 2-bromo-3-methylbutanoate according to Method C.