Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][CH2:11][S:12][CH2:13][C:14](=[O:16])[CH3:15])=[CH:9][C:4]=2[O:3][CH2:2]1.ClC1C=CC=C(C(OO)=[O:25])C=1.C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)(Cl)Cl>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][CH2:11][S:12]([CH2:13][C:14](=[O:16])[CH3:15])=[O:25])=[CH:9][C:4]=2[O:3][CH2:2]1
Reactant: CC(=O)CSCCc1ccc2c(c1)OCO2
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: CC(=O)CS(=O)CCc1ccc2c(c1)OCO2
Temperature: 0 °C
Reaction time: 0.67 h
Yield: 82 %

Procedure:
4 g of [{2-(1,3-benzodioxol-5-yl)ethyl}thio]propan-2-one was dissolved in 70 ml of chloroform. 3.2 g of 90% m-chloroperbenzoic acid was added to the solution under cooling with ice/water. The mixture was stirred for 40 min. 150 ml of chloroform and an aqueous sodium carbonate solution were added to the reaction mixture. After separation of the layers thus formed, the chloroform layer was washed with water three times and dried over anhydrous sodium sulfate. The solvent was distilled off and the residue was recrystallized from isopropyl ether to obtain 3.5 g of the intended compound in the form of colorless crystals.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]([CH3:12])[CH2:7]2.[N:13]([C:16]1[C:24]([I:25])=[CH:23][C:19]([C:20](O)=[O:21])=[C:18]([O:26][CH3:27])[CH:17]=1)=[N+:14]=[N-:15]>>[CH3:12][N:6]1[CH2:5][CH2:4][C:3]2[C:8](=[CH:9][CH:10]=[CH:11][C:2]=2[NH:1][C:20](=[O:21])[C:19]2[CH:23]=[C:24]([I:25])[C:16]([N:13]=[N+:14]=[N-:15])=[CH:17][C:18]=2[O:26][CH3:27])[CH2:7]1
Reactant: COc1cc(N=[N+]=[N-])c(I)cc1C(=O)O
Reactant: CN1CCc2c(N)cccc2C1
Product: COc1cc(N=[N+]=[N-])c(I)cc1C(=O)Nc1cccc2c1CCN(C)C2

Procedure:
The title compound was prepared in an analogous manner to Example 1 from 5-amino-2-methyl-1,2,3,4-tetrahydroisoquinoline and 4-azido-5-iodo-2-methoxybenzoic acid.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([Cl:10])[C:3]=1[CH2:4]Cl.[CH3:11][O:12][C:13](=[O:32])[C@H:14]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([OH:30])=[C:26]([OH:31])[CH:25]=1)[NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17].C([O-])([O-])=O.[K+].[K+]>[N+](CCCC)(CCCC)(CCCC)CCCC.[I-].CN(C=O)C.O>[CH3:11][O:12][C:13](=[O:32])[C@H:14]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][CH2:4][C:3]2[C:2]([Cl:1])=[CH:9][CH:8]=[CH:7][C:6]=2[Cl:10])=[C:26]([O:31][CH2:4][C:3]2[C:2]([Cl:1])=[CH:9][CH:8]=[CH:7][C:6]=2[Cl:10])[CH:25]=1)[NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:20])[CH3:21])=[O:17]
Reactant: ClCc1c(Cl)cccc1Cl
Reactant: COC(=O)[C@H](Cc1ccc(O)c(O)c1)NC(=O)OC(C)(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)[C@H](Cc1ccc(OCc2c(Cl)cccc2Cl)c(OCc2c(Cl)cccc2Cl)c1)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 71.8 %

Procedure:
2,6-Dichlorobenzyl chloride (1.73 g) was added to a suspension of N-(tert-butoxycarbonyl)-3,4-dihydroxy-L-phenylalanine methyl ester (2.5 g), K2CO3 (2.22 g), and n-Bu4NI (0.297 g) in DMF (15 mL) at room temperature. The mixture was stirred overnight at room temperature, diluted with water and extracted with ether. The extract was dried (MgSO4) and evaporated. The residue was purified by column chromatography (silica gel; eluent: hexanes/CH2Cl2/EtOAc, 5:5:1) to yield N-(tert-butoxycarbonyl)-3,4-bis(2,6-dichlorobenzyloxy)-L-phenylalanine methyl ester (2.0 g), ESMS: m/z 630 (MH+), N-(tert-butoxycarbonyl)-3-(2,6-dichlorobenzyloxy) -4-hydroxy-L-phenylalanine methyl ester (0.39 g), ESMS: m/z 470 (MH+), and N-(tert-butoxycarbonyl)-4-(2,6-dichlorobenzyloxy)-3-hydroxy-L-phenylalanine methyl ester (0.45 g), ESMS: m/z 470 (MH+), respectively.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH2:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][N:19]2[CH2:23][C@@H:22]([C:24]3[CH:35]=[CH:34][C:27]4[O:28][C:29]([CH3:33])([CH3:32])[O:30][CH2:31][C:26]=4[CH:25]=3)[O:21][C:20]2=[O:36])[CH:5]=[CH:6][CH:7]=1.[N+:37]([C:40]1[CH:41]=[C:42]([CH:46]=[CH:47][CH:48]=1)[C:43](Cl)=[O:44])([O-:39])=[O:38].C(=O)(O)[O-].[Na+]>N1C=CC=CC=1>[CH3:33][C:29]1([CH3:32])[O:28][C:27]2[CH:34]=[CH:35][C:24]([C@H:22]3[O:21][C:20](=[O:36])[N:19]([CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][O:12][CH2:11][CH2:10][O:9][CH2:8][C:4]4[CH:3]=[C:2]([NH:1][C:43](=[O:44])[C:42]5[CH:46]=[CH:47][CH:48]=[C:40]([N+:37]([O-:39])=[O:38])[CH:41]=5)[CH:7]=[CH:6][CH:5]=4)[CH2:23]3)=[CH:25][C:26]=2[CH2:31][O:30]1
Reactant: O=C(Cl)c1cccc([N+](=O)[O-])c1
Reactant: CC1(C)OCc2cc([C@@H]3CN(CCCCCCOCCOCc4cccc(N)c4)C(=O)O3)ccc2O1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Product: CC1(C)OCc2cc([C@@H]3CN(CCCCCCOCCOCc4cccc(NC(=O)c5cccc([N+](=O)[O-])c5)c4)C(=O)O3)ccc2O1
Reaction time: 2.5 h
Yield: 73.8 %

Procedure:
A solution of (5R)-3-{6-[2-{[(3-aminophenyl)methyl]oxy}ethoxy]hexyl}-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one (2.20 g) in pyridine (20 ml) under nitrogen was treated with 3-nitrobenzoyl chloride (819 mg) and the mixture was stirred at 20° for 2.5 h. Sat. sodium bicarbonate solution (100 ml) was added and the mixture was extracted with dichloromethane (2×50 ml). The combined extracts were dried (Na2SO4) and the solvent evaporated in vacuo. The residue was purified by flash chromatography on silica gel. Elution with EtOAc-PE (2:1) gave the title compound (2.11 g). LCMS RT=3.71 min, ES+ve 648 (MH)+.
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([OH:11])=O.S(Cl)(Cl)=O.[NH2:16][C:17]1[CH:18]=[C:19]([N:23]2[C:29](=[O:30])[CH2:28][C:27](=[O:31])[NH:26][C:25]3[C:32]4[C:37]([CH:38]=[CH:39][C:24]2=3)=[CH:36][CH:35]=[CH:34][CH:33]=4)[CH:20]=[CH:21][CH:22]=1>>[I:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([NH:16][C:17]1[CH:18]=[C:19]([N:23]2[C:29](=[O:30])[CH2:28][C:27](=[O:31])[NH:26][C:25]3[C:32]4[C:37]([CH:38]=[CH:39][C:24]2=3)=[CH:36][CH:35]=[CH:34][CH:33]=4)[CH:20]=[CH:21][CH:22]=1)=[O:11]
Reactant: O=C(O)Cc1ccccc1I
Reactant: Nc1cccc(N2C(=O)CC(=O)Nc3c2ccc2ccccc32)c1
Solvent: O=S(Cl)Cl
Product: O=C(Cc1ccccc1I)Nc1cccc(N2C(=O)CC(=O)Nc3c2ccc2ccccc32)c1
Yield: 23.2 %

Procedure:
2-Iodophenylacetic acid (39 mg, 0.15 mmol) was treated with thionyl chloride in the same manner as that of Example 13, and then by using the resultant together with 5-(3-aminophenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione (32 mg, 0.1 mmol) obtained in Example 53, (1), the title compound (13 mg, yield 23%) was obtained as pale brown powder in the same manner as that of Example 1, (4).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[F:14])[N:5]=[CH:4][N:3]=1.[CH2:15]([OH:18])[C:16]#[CH:17].[H-].[Na+].O>CN(C)C=O>[F:14][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=1[C:6]1[CH:7]=[C:2]([O:18][CH2:15][C:16]#[CH:17])[N:3]=[CH:4][N:5]=1
Reactant: Fc1ccccc1-c1cc(Cl)ncn1
Reactant: C#CCO
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: C#CCOc1cc(-c2ccccc2F)ncn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 73.3 %

Procedure:
In 5 ml of N,N-dimethylformamide were dissolved 212 mg of 4-chloro-6-(2-fluorophenyl)pyrimidine and 68 mg of 2-propyn-1-ol, to which 49 mg of sodium hydride (60% in oil) was added, followed by stirring at room temperature for 8 hours. The reaction mixture was then poured into water and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The resulting residue was subjected to silica gel column chromatography to give 170 mg of 4-(2-fluorophenyl)-6-(2-propynyloxy)pyrimidine (the present compound (54)).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:18]=[CH:19][CH:20]=1)[C:7]([C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[NH:11][CH:10]=1)=[O:8])([O-:3])=[O:2].Br[CH2:22][CH2:23][CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26].C(=O)([O-])[O-].[K+].[K+].Cl>CN(C)C=O.C(OCC)(=O)C>[N+:1]([C:4]1[CH:5]=[C:6]([CH:18]=[CH:19][CH:20]=1)[C:7]([C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]([CH2:22][CH2:23][CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH:10]=1)=[O:8])([O-:3])=[O:2]
Reactant: CCOC(=O)CCCBr
Reactant: O=C(c1cccc([N+](=O)[O-])c1)c1c[nH]c2ccccc12
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOC(=O)CCCn1cc(C(=O)c2cccc([N+](=O)[O-])c2)c2ccccc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 90.8 %

Procedure:
A mixture of 3-(3-nitrobenzoyl)indole (2.09 g), ethyl 4-bromobutyrate (1.614 g) and potassium carbonate (3.118 g) in N,N-dimethylformamide (20 ml) was stirred at 25° C. overnight. The reaction mixture was poured into a mixture of ethyl acetate and 1N hydrochloric acid. The organic layer was separated, washed with water and brine, and dried over magnesium sulfate. After evaporation of solvent, the crystalline residue was recrystallized from a mixture of ethyl acetate and hexane to give ethyl 4-[3-(3-nitrobenzoyl)indol-1-yl]butyrate (2.71 g) as colorless crystals.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[C:13]([F:21])=[C:14]([F:20])[C:15]4[N:16]=[CH:17][O:18][C:19]=4[C:11]=3[N:10]([S:22]([CH:25]3[CH2:27][CH2:26]3)(=[O:24])=[O:23])C2=O)=[C:4]([F:29])[CH:3]=1.[K].F[C:32]1C2N=COC=2C(NS(C2CC2)(=O)=O)=C(NC2C=CC(I)=CC=2F)C=1F>>[F:20][C:14]1[C:15]2[N:16]=[C:17]([CH3:32])[O:18][C:19]=2[C:11]([NH:10][S:22]([CH:25]2[CH2:27][CH2:26]2)(=[O:23])=[O:24])=[C:12]([NH:8][C:5]2[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=2[F:29])[C:13]=1[F:21]
Reactant: O=c1n(-c2ccc(Br)cc2F)c2c(F)c(F)c3ncoc3c2n1S(=O)(=O)C1CC1
Reactant: O=S(=O)(Nc1c(Nc2ccc(I)cc2F)c(F)c(F)c2ncoc12)C1CC1
Agent: [K]
Product: Cc1nc2c(F)c(F)c(Nc3ccc(Br)cc3F)c(NS(=O)(=O)C3CC3)c2o1

Procedure:
Compound 1G was prepared from 6-(4-bromo-2-fluoro-phenyl)-8-cyclopropanesulfonyl-4,5-difluoro-6,8-dihydro-imidazo[4′,5′:3,4]benzo[1,2-d]oxazol-7-one (I-25a: 120 mg, 0.245 mmol) and potassium trimethylsilonolate (46 mg, 0.368 mmol) using procedures analogous to those described above for Compound 1A to afford 20 mg of the product (17.8% yield). H1NMR (DMSO-d6, 300 MHz): δ 9.75 (s, 1H), 8.90 (s, 1H), 7.80 (s, 1H), 7.52 (dd, 1H), 7.17 (d, 1H), 6.80-6.68 (m, 1H), 2.68-2.60 (m, 1H), 0.90-0.82 (m, 2H), 0.80-0.70 (m, 2H). LCMS: 96.25%, m/z=460.0 (M−2). HPLC: 96.94%
Reaction SMILES: [BH4-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10](=[O:28])[CH:11]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=1)[C:12]([O:14][CH2:15][CH3:16])=[O:13].Cl>C(OCC)C.[Cl-].[Zn+2].[Cl-]>[F:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH:10]([OH:28])[CH:11]([CH2:17][C:18]1[CH:19]=[CH:20][C:21]([C:24]([F:26])([F:27])[F:25])=[CH:22][CH:23]=1)[C:12]([O:14][CH2:15][CH3:16])=[O:13]
Reactant: CCOC(=O)C(Cc1ccc(C(F)(F)F)cc1)C(=O)c1ccccc1F
Agent: Cl
Agent: [BH4-]
Agent: [Cl-]
Solvent: CCOCC
Product: CCOC(=O)C(Cc1ccc(C(F)(F)F)cc1)C(O)c1ccccc1F
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 80.6 %

Procedure:
To a solution of zinc chloride (14.8 g, 108.6 mmol) in diethyl ether (150 ml) was added sodium borohydride (8.22 g, 217 mmol) and the mixture was stirred at room temperature for 30 min. The insoluble material was filtered off. To the filtrate was added a solution of ethyl 3-(2-fluorophenyl)-3-oxo-2-((4-(trifluoromethyl)phenyl)methyl)propionate (20 g, 54.3 mmol) in diethyl ether (50 ml) and the mixture was stirred at room temperature for 30 min. 1N Hydrochloric acid was added to the reaction solution under ice-cooling for quenching, water (200 ml was added, and the mixture was extracted with ethyl acetate (300 ml×2). The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1-4:1) to give ethyl (2RS,3RS)-3-(2-fluorophenyl)-3-hydroxy-2-((4-(trifluoromethyl)phenyl)methyl)propionate (16.2 g, 81%) as a colorless oil.
Reaction SMILES: [C:1]1(=[O:7])[O:6][C:4](=[O:5])[CH:3]=[CH:2]1.[CH2:8]([NH:11][CH2:12][CH:13]=[CH2:14])[CH:9]=[CH2:10].[13CH4]>C1(C)C=CC=CC=1>[CH2:8]([N:11]([CH2:12][CH:13]=[CH2:14])[C:1](=[O:7])/[CH:2]=[CH:3]\[C:4]([OH:6])=[O:5])[CH:9]=[CH2:10]
Reactant: C=CCNCC=C
Reactant: O=C1C=CC(=O)O1
Agent: [13CH4]
Solvent: Cc1ccccc1
Product: C=CCN(CC=C)C(=O)/C=C\C(=O)O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Maleic anhydride (100 g, 1.02 mol) was dispersed in 400 mL toluene at 40° C. Diallylamine (97% pure, 100 g, 1.00 mol) was added over a period of 30 minutes with cooling so that the reaction temperature was maintained below 40° C. After addition, the reaction mixture was stirred at room temperature for 3 hours. The IR of the reaction mixture showed the absence of the anhydride. A nearly quantitative conversion was obtained. The Carbon-13 data is shown in Table 1.
Reaction SMILES: [NH2:1][C:2]1([CH2:8][OH:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.[F:10][C:11]1[CH:12]=[N:13][C:14]([O:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([S:27][CH3:28])[CH:22]=2)=[C:15]([CH:19]=1)[C:16](O)=[O:17].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O.C(N(CC)CC)C>[F:10][C:11]1[CH:12]=[N:13][C:14]([O:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([S:27][CH3:28])[CH:22]=2)=[C:15]([CH:19]=1)[C:16]([NH:1][C:2]1([CH2:8][OH:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1)=[O:17]
Reactant: NC1(CO)CCCCC1
Reactant: CSc1cccc(Oc2ncc(F)cc2C(=O)O)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CSc1cccc(Oc2ncc(F)cc2C(=O)NC2(CO)CCCCC2)c1
Temperature: 25 °C
Reaction time: 64 h
Yield: 62.7 %

Procedure:
A solution of (1-aminocyclohexyl)-methanol (R. J. W. Cremlyn et al J. Chem. Soc Perkins I, 1972, 1727) (130 mg, 0.78 mmol) and triethylamine (300 μl) in dimethylformamide (5 ml) was added to a solution of 5-fluoro-2-(3-methylsulfanyl-phenoxy)-nicotinic acid (218 mg, 0.78 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (165 mg, 0.86 mmol) and 1-hydroxybenzotriazole (116 mg, 0.86 mmol) in dimethylformamide (4 ml) and the reaction was stirred under nitrogen at room temperature for 64 h. The reaction mixture was concentrated under reduced pressure, and the residue was partitioned between ethyl acetate (25 ml) and water (25 ml). The organic phase was removed and washed with sat. sodium bicarbonate solution (25 ml) followed by 1M citric acid (25 ml) and brine (25 ml). The organic layer was dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with a solvent gradient of ethyl acetate:pentane (20:80 changing to 30:70 then 50:50, by volume) to give 5-fluoro-N-(1-hydroxymethyl-cyclohexyl)-2-(3-methylsulfanyl-phenoxy)-nicotinamide (191 mg) as a colourless oil.
Reaction SMILES: C(OC([NH:8][CH:9]([CH3:40])[C:10]([NH:12][CH:13]([C:36]([O:38][CH3:39])=[O:37])[CH2:14][C:15]1[CH:35]=[CH:34][C:18]([O:19][C:20]2[CH:33]=[CH:32][C:23]([CH2:24][CH:25]3[S:29][C:28](=[O:30])[NH:27][C:26]3=[O:31])=[CH:22][CH:21]=2)=[CH:17][CH:16]=1)=[O:11])=O)(C)(C)C.[ClH:41]>ClCCl>[ClH:41].[NH2:8][CH:9]([CH3:40])[C:10]([NH:12][CH:13]([C:36]([O:38][CH3:39])=[O:37])[CH2:14][C:15]1[CH:35]=[CH:34][C:18]([O:19][C:20]2[CH:33]=[CH:32][C:23]([CH2:24][CH:25]3[S:29][C:28](=[O:30])[NH:27][C:26]3=[O:31])=[CH:22][CH:21]=2)=[CH:17][CH:16]=1)=[O:11]
Reactant: COC(=O)C(Cc1ccc(Oc2ccc(CC3SC(=O)NC3=O)cc2)cc1)NC(=O)C(C)NC(=O)OC(C)(C)C
Agent: Cl
Solvent: ClCCl
Product: COC(=O)C(Cc1ccc(Oc2ccc(CC3SC(=O)NC3=O)cc2)cc1)NC(=O)C(C)N
Yield: 66.3 %

Procedure:
A solution of 5-[4-(4-(2-(2-t-butoxycarbonylaminopropanamido}2-methoxycarbonylethyl)phenoxy)benzyl]thiazolidin-2,4-dione (1 g, 1.75 mmol) in dichloromethane (10 ml) was bubbled with HCl gas at −10° C. for 50 minutes. The excess HCl gas was removed by N2 bubbling and concentrated to dryness to afford the title compound (0.59 g, yield 66.3%).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:13]2[C@H:22]3[C@H:17]([CH2:18][CH2:19][CH2:20][CH2:21]3)[C:16](=[O:23])[NH:15][N:14]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH2:11][CH3:12])[CH3:2].Cl[CH2:25][C:26]1[CH:34]=[CH:33][C:29]([C:30]([OH:32])=[O:31])=[CH:28][CH:27]=1.COC1C=C(C2[C@H]3[C@H](CCCC3)C(=O)N(CC3C=CC(C(O)=O)=CC=3)N=2)C=CC=1OC>>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:13]2[C@H:22]3[C@H:17]([CH2:18][CH2:19][CH2:20][CH2:21]3)[C:16](=[O:23])[N:15]([CH2:25][C:26]3[CH:34]=[CH:33][C:29]([C:30]([OH:32])=[O:31])=[CH:28][CH:27]=3)[N:14]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH2:11][CH3:12])[CH3:2]
Reactant: CCOc1ccc(C2=NNC(=O)[C@H]3CCCC[C@@H]23)cc1OCC
Reactant: O=C(O)c1ccc(CCl)cc1
Agent: COc1ccc(C2=NN(Cc3ccc(C(=O)O)cc3)C(=O)[C@H]3CCCC[C@@H]23)cc1OC
Product: CCOc1ccc(C2=NN(Cc3ccc(C(=O)O)cc3)C(=O)[C@H]3CCCC[C@@H]23)cc1OCC

Procedure:
Prepared from compound 7 and 4-chloromethylbenzoic acid as described for compound 83. Purified by chromatography (dichloromethane). Crystallized from diethyl ether. M.p. 152°-154° C.
Reaction SMILES: [CH3:1][C:2]1[C:3]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[C:4]([NH:8][C:9]([NH2:11])=S)[CH:5]=[CH:6][CH:7]=1.O.O.O.C([O-])(=O)C.[Pb+2].C([O-])(=O)C.[OH-].[K+]>O>[CH3:1][C:2]1[C:3]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[C:4]([NH:8][C:9]#[N:11])[CH:5]=[CH:6][CH:7]=1
Reactant: Cc1cccc(NC(N)=S)c1N1CCOCC1
Agent: CC(=O)[O-]
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: Cc1cccc(NC#N)c1N1CCOCC1

Procedure:
A mixture of 1-(3-methyl-2-morpholinophenyl)thiourea (6 g) suspended in water (40 ml), lead acetate trihydrate (9 g) in water (40 ml), potassium hydroxide (13.5 g) in water (35 mol) was heated at 90°-95° C. for 1 hour to give N-(3-methyl-2-morpholinophenyl)cyanamide (m.p. 137°-138° C.) which was recrystallised from ethyl acetate.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][O:10][C:11]2[C:19]([F:20])=[CH:18][C:14]([C:15]([OH:17])=[O:16])=[C:13]([F:21])[CH:12]=2)[CH:5]=[N:6][C:7]=1Cl.[H-].[Na+].[CH:24]([OH:27])([CH3:26])[CH3:25].Cl>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][O:10][C:11]2[C:19]([F:20])=[CH:18][C:14]([C:15]([OH:17])=[O:16])=[C:13]([F:21])[CH:12]=2)[CH:5]=[N:6][C:7]=1[O:27][CH:24]([CH3:26])[CH3:25]
Reactant: O=C(O)c1cc(F)c(OCc2cnc(Cl)c(Cl)c2)cc1F
Reactant: CC(C)O
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)Oc1ncc(COc2cc(F)c(C(=O)O)cc2F)cc1Cl
Temperature: 80 °C
Reaction time: 18 h
Yield: 46 %

Procedure:
To a solution of 4-((5,6-dichloropyridin-3-yl)methoxy)-2,5-difluorobenzoic acid (Preparation 14, 210 mg, 0.67 mmol) in THF (5 mL) was added an oil dispersion of NaH (60%, 157 mg, 3.93 mmol) followed by iso-propanol (5 mL) and the reaction mixture was warmed to 80° C. and stirred for 18 hours under a nitrogen atmosphere. Aqueous hydrogen chloride solution (1 M, 20 mL) was added and the mixture extracted with EtOAc (3×30 mL). The combined organics were dried over magnesium sulfate and the solvent was removed in vacuo. The resulting crude was purified by reverse phase chromatography eluting with H2O/MeCN/HCOOH (95/5/0.1 to 5/95/0.1, Biotage™ 40 g C18-silica gel) to yield the title compound (105 mg, 46%).
Reaction SMILES: C(C1[S:7][C:6]([C:8](=[O:19])[CH2:9][C:10](=[O:18])[C:11]([F:17])([F:16])[C:12]([F:15])([F:14])[F:13])=[CH:5][CH:4]=1)#N.S(=O)(=O)(O)O.[C:25]([OH:28])(=[O:27])[CH3:26]>O>[C:25]([C:26]1[S:7][C:6]([C:8](=[O:19])[CH2:9][C:10](=[O:18])[C:11]([F:17])([F:16])[C:12]([F:13])([F:14])[F:15])=[CH:5][CH:4]=1)([OH:28])=[O:27]
Reactant: CC(=O)O
Reactant: N#Cc1ccc(C(=O)CC(=O)C(F)(F)C(F)(F)F)s1
Agent: O=S(=O)(O)O
Solvent: O
Product: O=C(O)c1ccc(C(=O)CC(=O)C(F)(F)C(F)(F)F)s1

Procedure:
A mixture of 1-(5-cyano-2-thienyl)-4,4,5,5,5-pentafluoro-1,3-pentanedione (0.78 g), sulfuric acid (9 ml) and acetic acid (10 ml) was refluxed for 2 hours. The cooled mixture was poured into 100 ml of water. The precipitation was filtered and washed with water. 1H NMR (CDCl3): 6.53 (s, 1 H); 7.57 (d, 1 H, J=4.1 Hz); 7.78 (d, 1 H, J=4.1 Hz).
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1.[Br:12]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:12][CH2:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1
Reactant: COC(=O)c1ccc(C)nc1
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)c1ccc(CBr)nc1

Procedure:
To a solution of methyl 6-methylnicotinate (50 g, 331 mmol) in carbon tetrachloride (625 mL), was added N-bromosuccinimide (59 g, 331 mmol). Further 1.0 g of benzoyl peroxide was added, the mixture was reacted at a temperature from 40 to 50° C. for 24 hours with irradiation of light from a projector.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[O:11][CH3:12])[C:6]#[N:7].C(N)(=[S:15])C>Cl.CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[O:11][CH3:12])[C:6]([NH2:7])=[S:15]
Reactant: CC(N)=S
Reactant: COc1ccc(C#N)cc1OC
Agent: Cl
Solvent: CN(C)C=O
Product: COc1ccc(C(N)=S)cc1OC
Temperature: 90 °C
Yield: 61.9 %

Procedure:
25 g of 3,4-dimethoxybenzonitrile and 23 g of thioacetamide were dissolved in 120 ml of 10% hydrochloric acid-DMF. The solution was heated at 90° C. for 3 hours. The solution was further heated at 130° C. for 5 hours to conduct a reaction. The solvent was removed by distillation. The residue was washed twice with 100 ml of diethyl ether. Similar washing was conducted with 100 ml of water. The resulting crystals were collected by filtration and dried. Recrystallization from methanol was conducted to obtain 18.7 g of 3,4-dimethoxythiobenzamide as light brown columnar crystals.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[C:7]2[OH:12].[C:13]1([CH3:23])[CH:18]=[CH:17][C:16]([S:19](Cl)(=[O:21])=[O:20])=[CH:15][CH:14]=1>N1C=CC=CC=1>[C:13]1([CH3:23])[CH:18]=[CH:17][C:16]([S:19]([NH:1][C:2]2[CH:11]=[CH:10][CH:9]=[C:8]3[C:3]=2[CH:4]=[CH:5][CH:6]=[C:7]3[OH:12])(=[O:21])=[O:20])=[CH:15][CH:14]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: Nc1cccc2c(O)cccc12
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)Nc2cccc3c(O)cccc23)cc1
Yield: 96 %

Procedure:
A solution of 1 mole 5-amino-1-naphthol in dry pyridine was stirred at 0° C. and treated portionwise with 1 mole of p-toluenesulfonyl chloride. When anaylsis showed that the 5-amino-1-naphthol was consumed the reaction mixture was poured onto a sufficient quantity of aqueous hydrogen chloride to neutralize the excess pyridine and allow separation of the product as a fine powder which was filtered, washed with water, and recrystallized from ethanol to obtain (96% yield) analytically pure 5-p-toluenesulfonamido-1-naphthol having a melting point of 182°-194° C. Next, 2.58 g. (4.00 mmol) of 4-(m-aminophenylsulfonamido)-N-[4-(2,4-di-tert-pentylphenoxy)butyl]-1-hydroxy-2-naphthamide were dissolved in 10 ml. dry pyridine and treated with 50 ml. 5:1 acid and 10 ml. concentrated hydrochloric acid. The clear solution was cooled to 0° C. and treated with a solution of 284 mg. (4.00 mmol) sodium nitrite in 3 ml. of ice water. The resulting orange solution was added rapidly to a solution of 1.25 g. (4.00 mmol) of the above sulfonamidonaphthol dissolved in 8 ml. dry pyridine and 50 ml. 5:1 acid, and cooled to 5° C. The orange dye formed immediately. After 40 minutes at 5°-10°, the dye was precipitated by adding 300 ml. ice water and adjusting the pH to 2 with concentrated HCl. The orange powder obtained by filtration was washed with 8 liters of water and dried to give 3.31 g. Compound 12. This compound was tested in a manner similar to that of Example 12A and the released dye was found to have a λ max of 555 nm. The Dmax of transferred image was 0.97.