Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[C:12]2[O:11][CH2:10][CH2:9][N:8]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.C([Li])CCC.CCCCCC.[C:31](=[O:33])=[O:32].[Cl-].[NH4+].Cl>O1CCCC1>[C:16]([O:15][C:13]([N:8]1[CH2:7][C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([C:31]([OH:33])=[O:32])[C:12]=2[O:11][CH2:10][CH2:9]1)=[O:14])([CH3:19])([CH3:18])[CH3:17]
Reactant: O=C=O
Reactant: CC(C)(C)OC(=O)N1CCOc2c(Br)cccc2C1
Agent: Cl
Agent: [Cl-]
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCOc2c(cccc2C(=O)O)C1
Temperature: 78 °C
Reaction time: 1 h
Yield: 22.5 %

Procedure:
To a solution of tert-butyl 9-bromo-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (200 mg, 0.605 mmol) in tetrahydrofuran (4 ml) was added 1.6N solution of n-butyllithium in hexane (0.396 ml, 0.634 mmol) at −78° C., and the mixture was stirred at 78° C. for 1 hr. At −78° C., pulverized dry ice (2 g) was added to the reaction mixture, and the mixture was stirred for 1 hr. Saturated aqueous ammonium chloride solution (5 ml) and 1N hydrochloric acid (5 ml) were added, and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate) to give the desired product (40.0 mg, 22.6%) as an oil.
Reaction SMILES: [CH3:1][C:2]1[C:3](=[O:32])[C@@H:4]2[CH:19]([NH:20][C:21](=[O:30])[CH2:22][O:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:18](=[O:31])[N:5]2[C:6]=1[C:7]([O:9][CH2:10][O:11][C:12](=[O:17])[C:13]([CH3:16])([CH3:15])[CH3:14])=[O:8].O1CCCC1.C(O)(=O)C>[Ni].C1(C)C=CC=CC=1.[Zn]>[CH3:1][CH:2]1[CH:6]([C:7]([O:9][CH2:10][O:11][C:12](=[O:17])[C:13]([CH3:14])([CH3:15])[CH3:16])=[O:8])[N:5]2[C:18](=[O:31])[CH:19]([NH:20][C:21](=[O:30])[CH2:22][O:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C@H:4]2[C:3]1=[O:32]
Reactant: CC1=C(C(=O)OCOC(=O)C(C)(C)C)N2C(=O)C(NC(=O)COc3ccccc3)[C@H]2C1=O
Agent: [Ni]
Agent: [Zn]
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: Cc1ccccc1
Product: CC1C(=O)[C@@H]2C(NC(=O)COc3ccccc3)C(=O)N2C1C(=O)OCOC(=O)C(C)(C)C
Reaction time: 1 h

Procedure:
Freshly prepared pivaloyloxymethyl 2-methyl-1-oxo-6-(2-phenoxyacetamido)carbapen-2-em-3-carboxylate (prepared from 200 mg. of pivaloyloxymethyl 2-diazo-3-methyl-1-beta-oxo-7-(2-phenoxyacetamido)ceph-3-em-4-carboxylate (incorporating a 2 g. Raney nickel treatment into the isolation step) was taken up in 1 ml. of tetrahydrofuran and added to a stirred slurry of 2 g. of specially activated zinc powder (Example 2), in 6 ml. of acetic acid containing 30% tetrahydrofuran maintained at 0°-5° C. After stirring for 1 hour at this temperature, the reaction mixture was diluted with toluene and evaporated to dryness in vacuo to yield pivaloyloxymethyl 2-methyl-1-oxo-6-(2-phenoxyacetamido)carbapenam-3-carboxylate [Rf 0.34 (9:1 chloroform:ethyl acetate; ir (CH2Cl2) 1790, 1750, 1680 cm-1 ].
Reaction SMILES: [SH:1][C:2]1[O:3][C:4]2[C:13]3[CH:12]([CH2:14][CH2:15][NH:16][C:17](=[O:19])[CH3:18])[CH2:11][CH2:10][C:9]=3[CH:8]=[CH:7][C:5]=2[N:6]=1.IC.[C:22](=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)C>[CH3:22][S:1][C:2]1[O:3][C:4]2[C:13]3[CH:12]([CH2:14][CH2:15][NH:16][C:17](=[O:19])[CH3:18])[CH2:11][CH2:10][C:9]=3[CH:8]=[CH:7][C:5]=2[N:6]=1
Reactant: CC(=O)NCCC1CCc2ccc3nc(S)oc3c21
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOCC
Solvent: CI
Product: CSc1nc2ccc3c(c2o1)C(CCNC(C)=O)CC3
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 71.5 %

Procedure:
N-[2-(2-Mercapto-7,8-dihydro-6H-indeno[5,4-d][1,3]oxazol-8-yl)ethyl]acetamide (108 mg, 0.391 mmol) was dissolved in N,N-dimethylformamide (4 mL), iodomethane (48.6 μL, 0.782 mmol) and potassium carbonate (59.4 mg, 0.430 mmol) were added, and the mixture was stirred at room temperature for 15 min. The reaction solution was diluted with diethyl ether, washed with saturated aqueous sodium hydrogencarbonate solution and saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=50/50→100/0) to give the title compound (81.2 mg, yield 72%).
Reaction SMILES: C([O:3][C:4](=[O:30])[C:5]1[CH:10]=[CH:9][C:8]([CH:11]([CH:24]2[CH2:27][C:26]([CH3:29])([CH3:28])[CH2:25]2)[NH:12][C:13]2[C:22]([CH3:23])=[CH:21][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:14]=2)=[CH:7][CH:6]=1)C.[OH-].[Na+].Cl>O1CCCC1.CO>[CH3:28][C:26]1([CH3:29])[CH2:25][CH:24]([CH:11]([NH:12][C:13]2[C:22]([CH3:23])=[CH:21][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:14]=2)[C:8]2[CH:7]=[CH:6][C:5]([C:4]([OH:30])=[O:3])=[CH:10][CH:9]=2)[CH2:27]1
Reactant: CCOC(=O)c1ccc(C(Nc2nc3ccccc3cc2C)C2CC(C)(C)C2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: Cc1cc2ccccc2nc1NC(c1ccc(C(=O)O)cc1)C1CC(C)(C)C1
Temperature: 50 °C
Yield: 91.5 %

Procedure:
(+/−)-4-[(3,3-dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoic acid ethyl ester (Intermediate 25) (43 mg, 0.11 mmol) was dissolved in tetrahydrofuran (3 mL) and methanol (1 mL), and 1.0 M NaOH (2 mL) was added. This was stirred at 50° C. at first as a suspension then as a clear solution for 4 h before cooling to room temperature. 1 N HCl was added until the solution was pH 5. This was extracted twice with ethyl acetate and the combined organics were dried over MgSO4. The solution was concentrated in vacuo to give (+/−)-4-[(3,3-dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoic acid (37.7 mg) as a white solid. MS (M+1): 375.1.
Reaction SMILES: C([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([OH:17])[CH:15]=2)[C:10]([CH3:18])=[N:9]1)C1C=CC=CC=1.O.Cl>C(O)C.[C].[Pd]>[CH3:18][C:10]1[C:11]2[C:16](=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=2)[NH:8][N:9]=1
Reactant: Cc1nn(Cc2ccccc2)c2cc(O)ccc12
Agent: [Pd]
Agent: Cl
Solvent: CCO
Solvent: O
Product: Cc1n[nH]c2cc(O)ccc12
Temperature: 60 °C
Reaction time: 10 h

Procedure:
1-Benzyl-3-methylindazol-6-ol (16.7410 g) and 10% palladium-carbon-PE-type-50% wet with water (5.1164 g; manufactured by N.E. Chemcat Corp.) were suspended in ethanol (166 mL), and then concentrated hydrochloric acid (5.83 mL; manufactured by Kanto Chemical Co., Inc.) was added thereto. The reaction system was purged with hydrogen, and under a hydrogen atmosphere, the reaction solution was stirred for 10 hours at 60° C. The reaction solution was cooled to room temperature, and then the reaction system was purged with nitrogen. 10% Palladium on carbon-PE-type-50% wet with water (1.5059 g; manufactured by N.E. Chemcat Corp.) was added to the reaction solution, and the reaction system was purged with hydrogen. Under a hydrogen atmosphere, the reaction solution was stirred for 5 hours at 60° C. The reaction solution was cooled to room temperature, and the reaction system was purged with nitrogen. Subsequently, the reaction solution was filtered, and the solvent was evaporated under reduced pressure from the filtrate. Ethyl acetate was added to the resulting residue, and the mixture was washed once with a saturated aqueous solution of sodium hydrogen carbonate. The organic layer was washed once with a saturated sodium hydrogen carbonate solution, and then was dried over sodium sulfate. The solvent was evaporated under reduced pressure from the organic layer, and thus the title compound was obtained as a crude product (10.816 g).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:18]=[CH:17][C:16]([C:19](=[O:32])[NH:20][C:21]3[S:22][C:23]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[N:24][N:25]=3)=[CH:15][CH:14]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:33]([O:35]CC)=[O:34].[OH-].[Na+].C(O)C>C1COCC1.C(OCC)(=O)C.Cl>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:14]=[CH:15][C:16]([C:19](=[O:32])[NH:20][C:21]3[S:22][C:23]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[N:24][N:25]=3)=[CH:17][CH:18]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:33]([OH:35])=[O:34]
Reactant: CCOC(=O)C1CCOc2cc(Oc3ccc(C(=O)Nc4nnc(-c5ccccc5)s4)cc3)c(Cl)cc21
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: CCO
Product: O=C(Nc1nnc(-c2ccccc2)s1)c1ccc(Oc2cc3c(cc2Cl)C(C(=O)O)CCO3)cc1
Reaction time: 4 h
Yield: 30.6 %

Procedure:
Ethyl 6-chloro-7-(4-(5-phenyl-1,3,4-thiadiazol-2-ylcarbamoyl)phenoxy)chroman-4-carboxylate (17 mg, 0.032 mmol) was diluted with THF (500 μL) followed by the addition of NaOH (159 μL, 0.16 mmol) and ethanol (200 μL). After stirring for 4 hours, the reaction was diluted with ethyl acetate and 1N HCl, the layers were separated and the organic layer was dried over MgSO4, filtered and concentrated. The material was purified using a 0.5 mm preparative TLC plate eluting with 10% methanol/DCM to yield the desired compound (5 mg, 0.0098 mmol, 31% yield). MS (ESI)=508.1 (M+1).
Reaction SMILES: [NH2:1][C:2]1[N:6]([CH2:7][CH2:8][OH:9])[N:5]=[C:4]([C:10]2[CH:15]=[CH:14][N:13]=[C:12]([NH:16][CH3:17])[CH:11]=2)[CH:3]=1.N1C=CN=C1.[C:23]([Si:27](Cl)([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)([CH3:26])([CH3:25])[CH3:24]>CN(C1C=CN=CC=1)C.CN(C=O)C>[NH2:1][C:2]1[N:6]([CH2:7][CH2:8][O:9][Si:27]([C:23]([CH3:26])([CH3:25])[CH3:24])([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:5]=[C:4]([C:10]2[CH:15]=[CH:14][N:13]=[C:12]([NH:16][CH3:17])[CH:11]=2)[CH:3]=1
Reactant: CNc1cc(-c2cc(N)n(CCO)n2)ccn1
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Agent: CN(C)c1ccncc1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CNc1cc(-c2cc(N)n(CCO[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)n2)ccn1
Reaction time: 8 h
Yield: 100 %

Procedure:
Starting material 2-(5-amino-3-(2-(methylamino)pyridin-4-yl)-1H-pyrazol-1-yl)ethanol 30.A was prepared analagously to example 23.1. To a flask with 30.A (306 mg, 1.3 mmol) was added DMAP (16 mg, 0.13 mmol), 1H-imidazole (268 mg, 3.9 mmol). Then DMF 1.5 mL was added, followed by tert-butylchlorodiphenylsilane (505 mg, 1.8 mmol). The reaction was stirred overnight. Standard aqueous workup and silica gel chromatography afforded 618 mg (100%) 30.B.
Reaction SMILES: [Br:1][C:2]1[C:3]([Cl:19])=[C:4]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH:5]=[C:6]([CH:8]([F:10])[F:9])[CH:7]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH3:30][O:31][C:32]1[CH:39]=[CH:38][C:35]([CH2:36]Cl)=[CH:34][CH:33]=1.[Li+].[Cl-]>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[C:3]([Cl:19])=[C:4]([N:11]([CH2:36][C:35]2[CH:38]=[CH:39][C:32]([O:31][CH3:30])=[CH:33][CH:34]=2)[C:12](=[O:18])[O:13][C:14]([CH3:15])([CH3:16])[CH3:17])[CH:5]=[C:6]([CH:8]([F:10])[F:9])[CH:7]=1
Reactant: COc1ccc(CCl)cc1
Reactant: CC(C)(C)OC(=O)Nc1cc(C(F)F)cc(Br)c1Cl
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Cl-]
Agent: [Li+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COc1ccc(CN(C(=O)OC(C)(C)C)c2cc(C(F)F)cc(Br)c2Cl)cc1
Reaction time: 8 h
Yield: 94.2 %

Procedure:
tert-Butyl (3-bromo-2-chloro-5-(difluoromethyl)phenyl)carbamate (1.82 g, 5.10 mmol) was dissolved in DMF (11.1 mL) at room temperature. NaHMDS (6.12 mL, 6.12 mmol) was added dropwise and the reaction was stirred for 30 minutes before the addition of 4-methoxybenzyl chloride (0.904 mL, 6.64 mmol) and stirring overnight. The reaction mixture was diluted with EtOAc causing a ppt to form. 10% aq. LiCl solution was added and the two layers became clear with stirring. The mixture was poured into a separatory funnel and the organic layer was washed with an extra equivalent of 10% aq. LiCl solution. The organic layer was dried over Na2SO4 and concentrated. Column chromatography (220 g SiO2, 0 to 8% EtOAc-hexane, gradient elution) afforded the expected product tert-butyl (3-bromo-2-chloro-5-(difluoromethyl)phenyl)(4-methoxybenzyl)carbamate (2.29 g).
Reaction SMILES: [Br-].[CH3:2][O:3][C:4]([CH2:6][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)=[O:5].[H-].[Na+].[N+:28]([C:31]1[CH:32]=[C:33]([CH:36]=[CH:37][C:38]=1[N:39]1[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1)[CH:34]=O)([O-:30])=[O:29]>C1COCC1.[Cl-].[Na+].O>[N+:28]([C:31]1[CH:32]=[C:33]([CH:34]=[CH:6][C:4]([O:3][CH3:2])=[O:5])[CH:36]=[CH:37][C:38]=1[N:39]1[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1)([O-:30])=[O:29]
Reactant: O=Cc1ccc(N2CCNCC2)c([N+](=O)[O-])c1
Reactant: COC(=O)C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [Cl-]
Agent: [H-]
Solvent: C1CCOC1
Solvent: O
Product: COC(=O)C=Cc1ccc(N2CCNCC2)c([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 16.5 h
Yield: 74.9 %

Procedure:
A solution of methoxycarbonylmethyl(triphenyl)phosphonium bromide (1.1 g, TCI) in THF (12.5 ml) was added with sodium hydride (115 mg, WAKO) under ice cooling, warmed to room temperature, then added dropwise with a solution of 3-nitro-4-(piperazin-1-yl)benzaldehyde (550.6 mg, MAYB) in THF (12.5 ml), and stirred at the same temperature for 16.5 hours. The reaction mixture was poured into brine (40 ml), and extracted with ethyl acetate (100 ml). The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate and saturated brine, and dried, and then the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane:ethyl acetate=5:1) to obtain the title compound (Intermediate Int. n-19, 511 mg).
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1.[CH2:14]([O:21][C:22]1[CH:23]=[CH:24][C:25]2[C:26]3[N:34]=[C:33](Br)[CH:32]=[C:31]([C:36]([O:38][CH3:39])=[O:37])[C:27]=3[NH:28][C:29]=2[CH:30]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:14]([O:21][C:22]1[CH:23]=[CH:24][C:25]2[C:26]3[N:34]=[C:33]([C:5]4[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:13])([F:12])[F:1])[CH:4]=4)[CH:32]=[C:31]([C:36]([O:38][CH3:39])=[O:37])[C:27]=3[NH:28][C:29]=2[CH:30]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: COC(=O)c1cc(Br)nc2c1[nH]c1cc(OCc3ccccc3)ccc12
Reactant: OB(O)c1cccc(C(F)(F)F)c1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: COc1cccc(OC)c1-c1ccccc1P(C1CCCCC1)C1CCCCC1
Product: COC(=O)c1cc(-c2cccc(C(F)(F)F)c2)nc2c1[nH]c1cc(OCc3ccccc3)ccc12
Temperature: 70 °C
Yield: 83.1 %

Procedure:
A mixture of 3-(trifluoromethyl)phenylboronic acid (0.59 g, 3.1 mmol), methyl 7-(benzyloxy)-2-bromo-5H-pyrido[3,2-b]indole-4-carboxylate (1.07 g, 2.60 mmol), powdered potassium phosphate tribasic (1.33 g, 6.24 mmol), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (0.214 g, 0.520 mmol), and Pd(OAc)2 (0.058 g, 0.260 mmol) in a microwave vial was flushed with nitrogen. THF (13 mL) was added, the vial was capped, and the reaction was heated in a 70° C. oil bath for 24 hr. It was partitioned between EtOAc and water. The organic phase was washed with water and brine, dried with sodium sulfate, and the solvent removed. Silica gel chromatography (step gradient elution with DCM containing 50 to 25% hexane) afforded methyl 7-(benzyloxy)-2-(3-(trifluoromethyl)phenyl)-5H-pyrido[3,2-b]indole-4-carboxylate (1.03 g, 2.16 mmol, 83% yield) as a tan solid. MS (ESI) m/z 477.1 (M+H). 1H NMR (500 MHz, chloroform-d) δ ppm 9.47 (1H, s), 8.44 (1H, s), 8.30-8.37 (2H, m), 8.21 (1H, s), 7.57-7.67 (2H, m), 7.49 (2H, d, J=7.32 Hz), 7.42 (2H, t, J=7.48 Hz), 7.32-7.38 (1H, m), 7.03-7.09 (2H, m), 5.21 (2H, s), 4.10 (3H, s).
Reaction SMILES: [C:1]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[CH:16]=[CH:17][C:18](=[N:20][OH:21])[CH3:19])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].C([O-])(O)=O.[Na+].II>O.OS([O-])=O.[Na+]>[C:1]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[O:21][N:20]=[C:18]([CH3:19])[CH:17]=1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2]
Reactant: CC(C=CC1CCCN1C(=O)OCc1ccccc1)=NO
Agent: II
Agent: O=C([O-])O
Agent: O=S([O-])O
Solvent: O
Product: Cc1cc([C@@H]2CCCN2C(=O)OCc2ccccc2)on1
Yield: 84.8 %

Procedure:
To a stirred solution of 6 g (20.83 mmol) of the oxime compound from step 24f above, in a wrapped flask to protect from light, was added 12.1 g (72.92 mmol) of Kl dissolved in 80 mL of water and, in small portions, 7 g (83.33 mmol) of NaHCO3 and 15.86 g (62.5 mmol) of iodine. The reaction was heated at reflux for 16 hr, cooled and diluted with saturated aq. NaHSO3. The solution was extracted with ether, and the extract was washed with saturated aq. NaHSO3, dried over Na2SO4, and concentrated to afford the title product (5.06 g, 85% yield). The compound was taken to the next step without further purification. IR 1702, 1604, 1444, 1417, 1356, 1173, 1103, 1079 cm-1.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([NH:11][NH:12][C:13](=O)[C:14]([N:16]([CH3:24])[CH2:17][C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)=[O:15])=[S:10])=[CH:4][CH:3]=1.C(=O)(O)[O-].[Na+]>CO.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:9]([SH:10])=[N:11][N:12]=[C:13]2[C:14]([N:16]([CH3:24])[CH2:17][C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)=[O:15])=[CH:4][CH:3]=1
Reactant: CN(Cc1ccncc1)C(=O)C(=O)NNC(=S)Nc1ccc(F)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CN(Cc1ccncc1)C(=O)c1nnc(S)n1-c1ccc(F)cc1
Temperature: 80 °C
Reaction time: 26 h
Yield: 15.4 %

Procedure:
A mixture of 2-(2-((4-fluorophenyl)carbamothioyl)hydrazinyl)-N-methyl-2-oxo-N-(pyridin-4-ylmethyl)acetamide (79) (0.75 g, 2.075 mmol) and sodium bicarbonate (0.35 g, 4.17 mmol) in methanol/water (1:1) (20 mL) was stirred at 80° C. for 26 h. After evaporation of solvent, the residue was extracted with dichloromethane/methanol (10:1) (3×60 mL). The combined organic phase was evaporated and the crude product was purified by flash column chromatography on silica gel (0%-20% MeOH in dichloromethane) to provide 4-(4-fluorophenyl)-5-mercapto-N-methyl-N-(pyridin-4-ylmethyl)-4H-1,2,4-triazole-3-carboxamide (80) as a white solid (0.11 g).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][C:20]=1[Cl:21])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11](F)=[C:10]([N+:15]([O-:17])=[O:16])[CH:9]=1)=[O:6].[Na].[CH3:23][OH:24]>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][C:20]=1[Cl:21])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:24][CH3:23])=[C:10]([N+:15]([O-:17])=[O:16])[CH:9]=1)=[O:6]
Reactant: O=C(Nc1ccc(F)c([N+](=O)[O-])c1)c1ccc(Cl)c(Cl)c1
Reactant: CO
Agent: [Na]
Product: COc1ccc(NC(=O)c2ccc(Cl)c(Cl)c2)cc1[N+](=O)[O-]

Procedure:
Prepared according to the procedure described for Example 10, Step A from 3,4-dichloro-N-3-nitro-4-fluorophenyl)-benzamide from Example 22, Step A (5.2 g, 20 mmol) and sodium (1.3 g, 57 mmol) using methanol in place of ethanol to afford the product (5.8 g). m.p. 215-218° C. after chromatography on silica gel in dichloromethane/methanol 99:1.
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](N)=[CH:4][CH:3]=1.C(OCC1OC1)(=O)C(C)=C>CO>[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: Nc1ccc(N)c2c1C(=O)c1ccccc1C2=O
Agent: C=C(C)C(=O)OCC1CO1
Solvent: CO
Product: O=C1c2ccccc2C(=O)c2ccccc21

Procedure:
A solution prepared by adding 0.02 part of methoquinone to a mixture comprising 24 parts of 1,4-diaminoanthraquinone and 70 parts of glycidyl methacrylate and dissolving the obtained mixture in 1000 parts of methanol was stirred under reflux for 8 hours. After the completion of the reaction, the reaction mixture was distilled to remove the methanol. The obtained viscous solid was subjected to extractive washing with petroleum ether to give a blue polymerizable anthraquinone dye D. The anthraquinone dye D is represented by the below chemical formula (V). ##STR5##
Reaction SMILES: [F:1][C:2]1[CH:11]=[C:10]([O:12][CH:13]([CH3:15])[CH3:14])[CH:9]=[CH:8][C:3]=1[C:4]([O:6]C)=[O:5].[OH-].[Li+]>C1COCC1.O>[F:1][C:2]1[CH:11]=[C:10]([O:12][CH:13]([CH3:15])[CH3:14])[CH:9]=[CH:8][C:3]=1[C:4]([OH:6])=[O:5]
Reactant: COC(=O)c1ccc(OC(C)C)cc1F
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)Oc1ccc(C(=O)O)c(F)c1
Temperature: 70 °C
Reaction time: 2 h
Yield: 120 %

Procedure:
To a mixture of methyl 2-fluoro-4-hydroxy-benzoate (2.1 g, 12.4 mmol), potassium carbonate (6.8 g, 49.5 mmol) in dry DMF (13 mL) was added 2-iodopropane (2.5 mL, 24.8 mmol) and the reaction mixture was heated at 60° C. for 2 hours. The reaction was cooled and diluted with ether (50 mL) and filtered over Celite®. The filtrate was washed sequentially with water (3×25 mL) and brine solution (25 mL). The organic layer was separated and dried over MgSO4 and solvent was concentrated in vacuo to give a residue which was purified by silica gel column chromatography using 5-45% EtOAc/hexanes to give methyl 2-fluoro-4-isopropoxybenzoate as a colorless oil (2.2 g, 83%). To a solution of methyl 2-fluoro-4-isopropoxybenzoate (2.2 g, 10.3 mmol) in THF (5.5 mL) was added a suspension of lithium hydroxide (0.9 g, 37.1 mmol) in water (5.5 mL). The reaction mixture was stirred at 70° C. for 2 hours. The reaction mixture was cooled to room temperature and the excess LiOH was removed by filtration. The filtrate was diluted with water (9 ml), and washed with ether (2×5 mL). The aqueous layer was separated and cooled to 0° C. and the pH was adjusted to pH 2 by addition of 6 M HCl solution. The aqueous layer was extracted with EtOAc (3×30 mL). The organics were separated and washed sequentially with water and brine. The organic layer was separated, dried and concentrated in vacuo to give 2-fluoro-4-isopropoxy-benzoic acid (2.45 g, 67%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.98 (t, J=8.8 Hz, 1H), 6.69 (ddd, J=15.1, 10.9, 2.0 Hz, 2H), 4.63 (dt, J=12.1, 6.0 Hz, 1H), 1.39 (d, J=6.1 Hz, 6H).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([C:12]2[CH:17]=[C:16]([N:18]3[C@@H:22]([CH2:23][O:24][Si](C(C)(C)C)(C4C=CC=CC=4)C4C=CC=CC=4)[C@H:21]([C:42]4[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][CH:43]=4)[O:20][C:19]3=[O:50])[N:15]=[C:14]([N:51]3[CH2:56][CH2:55][O:54][CH2:53][CH2:52]3)[N:13]=2)=[CH:4][N:3]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[NH2:1][C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([C:12]2[CH:17]=[C:16]([N:18]3[C@@H:22]([CH2:23][OH:24])[C@H:21]([C:42]4[CH:43]=[CH:44][C:45]([O:48][CH3:49])=[CH:46][CH:47]=4)[O:20][C:19]3=[O:50])[N:15]=[C:14]([N:51]3[CH2:52][CH2:53][O:54][CH2:55][CH2:56]3)[N:13]=2)=[CH:4][N:3]=1
Reactant: COc1ccc([C@@H]2OC(=O)N(c3cc(-c4cnc(N)nc4C(F)(F)F)nc(N4CCOCC4)n3)[C@H]2CO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: COc1ccc([C@@H]2OC(=O)N(c3cc(-c4cnc(N)nc4C(F)(F)F)nc(N4CCOCC4)n3)[C@H]2CO)cc1
Yield: 50.6 %

Procedure:
To a solution of (4S,5S)-3-(2′-amino-2-morpholino-4′-(trifluoromethyl)-[4,5′-bipyrimidin]-6-yl)-4-(((tert-butyldiphenylsilyl)oxy)methyl)-5-(4-methoxyphenyl)oxazolidin-2-one (68 mg, 65 μmol) in THF (2 mL) was added dopwise at 0° C. 1M TBAF in THF (0.05 ml, 0.05 mmol), and the resulting mixture was stirred for 30 min at 0° C. and 1 h at RT. The reaction mixture was concentrated, and the residue was purified by column chromatography using a ratio of hexane/CH2Cl2/MeOH from 100:100:5 to 0:100:5, followed by preparative HPLC (Waters Sun Fire C18, 30×100 mm, 5 um; 0.1% TFA-water/acetonitrile; gradient acetonitrile 30-50% in 20 min) to afford the title compound as white solid (18 mg, 50%); TLC (CH2Cl2/MeOH 19:1) Rf=0.40; tR=0.998 min (UPLC 1); LC-MS: [M+H] 548; Rt 0.96 min; (LCMS method 2). 1H NMR (600 MHz, DMSO-d6): 8.60 (s, 1H), 7.64 (br s, 2H), 7.53 (s, 1H), 7.34 (d, 2H), 7.00 (d, 2H), 5.58 (d, 1H), 5.32 (t, 1H), 4.59 (m, 1H), 4.00 (m, 1H), 3.82 (m, 1H), 3.76 (s, 3H), 3.75-3.55 (m, 81-1).