Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[CH2:2][CH2:3][CH2:4][C:5]1[C:6]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[N:7][N:8]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]3[N:20]=[C:21]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[O:22][C:23]=3[CH3:24])=[CH:13][CH:12]=2)[CH:9]=1.[C-:37]#[N:38].[Na+].CS(C)=O>O>[CH3:24][C:23]1[O:22][C:21]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[N:20][C:19]=1[CH2:18][O:17][C:14]1[CH:15]=[CH:16][C:11]([CH2:10][N:8]2[CH:9]=[C:5]([CH2:4][CH2:3][CH2:2][C:37]#[N:38])[C:6]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[N:7]2)=[CH:12][CH:13]=1
Reactant: [C-]#N
Reactant: Cc1oc(-c2ccccc2)nc1COc1ccc(Cn2cc(CCCI)c(-c3ccccc3)n2)cc1
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: Cc1oc(-c2ccccc2)nc1COc1ccc(Cn2cc(CCCC#N)c(-c3ccccc3)n2)cc1
Temperature: 60 °C
Reaction time: 2 h
Yield: 92.4 %

Procedure:
A mixture of 1-iodo-3-[1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-3-phenyl-1H-pyrazol-4-yl]propane (1.75 g), sodium cyanide (291 mg), and dimethyl sulfoxide (5 ml) was stirred at 60° C. for 2 hours. The reaction mixture was poured into water, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), and then concentrated. The residue was subjected to silica gel column chromatography, and 4-[1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-3-phenyl-1H-pyrazol-4-yl]butyronitrile (1.34 g, yield: 92%) was obtained as a colorless oily substance from the fraction eluted with ethyl acetate-hexane (2:3, volume ratio).
Reaction SMILES: [NH2:1][C@@H:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[N:4]([CH2:19][C:20]([F:23])([F:22])[F:21])[C:3]1=[O:24].C(N(CC)CC)C.[CH:32]([C:35]1[NH:36][C:37](=[O:46])[N:38]([CH:40]2[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]2)[CH:39]=1)([CH3:34])[CH3:33].[O:47]1CCC[CH2:48]1>>[CH:32]([C:35]1[NH:36][C:37](=[O:46])[N:38]([CH:40]2[CH2:45][CH2:44][N:43]([C:48]([NH:1][C@@H:2]3[N:8]=[C:7]([C:9]4[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=4)[C:6]4[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=4[N:4]([CH2:19][C:20]([F:21])([F:23])[F:22])[C:3]3=[O:24])=[O:47])[CH2:42][CH2:41]2)[CH:39]=1)([CH3:34])[CH3:33]
Reactant: C1CCOC1
Reactant: CC(C)c1cn(C2CCNCC2)c(=O)[nH]1
Reactant: N[C@@H]1N=C(c2ccccc2)c2ccccc2N(CC(F)(F)F)C1=O
Solvent: CCN(CC)CC
Product: CC(C)c1cn(C2CCN(C(=O)N[C@@H]3N=C(c4ccccc4)c4ccccc4N(CC(F)(F)F)C3=O)CC2)c(=O)[nH]1
Reaction time: 1 h

Procedure:
(3R)-3-Amino-5-phenyl-1-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one (127 mg, 0.382 mmol) (Y.-J. Shi et al., Tetrahedron, 1999, 55, 909-918) and triethylamine (0.053 mL, 0.382 mmol) were added to a solution of p-nitrophenylchloroformate (77 mg, 0.382 mmol) in tetrahydrofuran (45 mL) at 0° C. After 1 h, additional triethylamine was added (0.106 mL, 0.764 mmol) along with 4-isopropyl-1-piperidin-4-yl-1,3-dihydro-2H-imidazol-2-one (80 mg, 0.382 mmol). The reaction stirred at 0 oC for 10 min and was then heated to 50oC. After 2 h, the reaction was concentrated and redissolved in ethyl acetate. The organics were washed with 1 N sodium hydroxide solution (3×), water, brine, and dried over magnesium sulfate. Purification by silica gel chromatography (100% dichloromethane=10% methanol/dichloromethane) gave 100 mg of the titled compound. MS 569.24 (M+1).
Reaction SMILES: N[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=1.[N+:9]([O-])([OH:11])=[O:10].N.S(=O)(=O)(O)[OH:15]>>[OH:15][C:2]1[C:7]([N+:9]([O-:11])=[O:10])=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=1
Reactant: O=S(=O)(O)O
Reactant: O=[N+]([O-])O
Reactant: Cc1ccc(N)nc1
Agent: N
Product: Cc1cnc(O)c([N+](=O)[O-])c1
Temperature: 130 °C

Procedure:
25 g of 2-amino-5-methylpyridine are dissolved in 50 cm3 of concentrated sulfuric acid in a 600 cm3 round- bottomed flask. A mixture consisting of 40 cm3 of concentrated nitric acid and 40 cm3 of concentrated sulfuric acid is progressively added. The reaction mixture heats up with formation of foam. The temperature is maintained constant at 130° C. throughout the duration of the addition of the acid. The colored solution is then poured onto 300 g of ice and the pH is brought to around 3-4 by addition of aqueous ammonia. After standing in a refrigerator, the precipitate obtained is collected on a filter, washed with water and dried. It is recrystallized from hot water.
Reaction SMILES: [C:1]1([C:7]2[N:8]=[C:9]([C:19]([O:21][CH2:22][CH3:23])=[O:20])N=N[C:12]=2[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:24](N1CCCC1)=[CH2:25]>C(Cl)(Cl)Cl>[C:13]1([C:12]2[CH:24]=[CH:25][C:9]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[N:8][C:7]=2[C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: CCOC(=O)c1nnc(-c2ccccc2)c(-c2ccccc2)n1
Reactant: C=CN1CCCC1
Solvent: ClC(Cl)Cl
Product: CCOC(=O)c1ccc(-c2ccccc2)c(-c2ccccc2)n1

Procedure:
General Procedure D. Ethyl 5,6-diphenyl-1,2,4-triazine-3-carboxylate (Compound 11, 200 mg, 0.66 mmol) and crude 1-vinylpyrrolidine (Compound 38, 2 g) in CHCl3 (20 ml) was heated at 75° C. overnight under nitrogen. The solvent was removed in vacuo, and the residue was purified by silica gel column chromatography (20% ethyl acetate in hexane) to yield the title compound as a light yellow solid.
Reaction SMILES: [C:1]1([C@@H:7]([NH:9][C:10]2[N:15]=[C:14]([N:16]3[C:20]4[CH:21]=[C:22]([N:25]=[N+:26]=[N-:27])[CH:23]=[CH:24][C:19]=4[N:18]=[CH:17]3)[CH:13]=[CH:12][N:11]=2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:28]([O:30][C:31](=[O:38])[CH:32]=[C:33](NC)NC)[CH3:29]>O1CCOCC1>[C:1]1([C@@H:7]([NH:9][C:10]2[N:15]=[C:14]([N:16]3[C:20]4[CH:21]=[C:22]([N:25]5[CH:33]=[C:32]([C:31]([O:30][CH2:28][CH3:29])=[O:38])[N:27]=[N:26]5)[CH:23]=[CH:24][C:19]=4[N:18]=[CH:17]3)[CH:13]=[CH:12][N:11]=2)[CH3:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: C[C@H](Nc1nccc(-n2cnc3ccc(N=[N+]=[N-])cc32)n1)c1ccccc1
Reactant: CCOC(=O)C=C(NC)NC
Solvent: C1COCCO1
Product: CCOC(=O)c1cn(-c2ccc3ncn(-c4ccnc(N[C@@H](C)c5ccccc5)n4)c3c2)nn1

Procedure:
The title compound was prepared from 266 mg of 2-[(S)-1-phenylethylamino]-4-[6-azidobenzimidazol-1-yl]pyrimidine, about 100 μL ethyl-3,3-dimethylaminoacrylate and 5 mL 1,4-dioxane using the procedure described in EXAMPLE 276 to give 283 mg of the title compound. RF: 0.4 (5% MeOH in CH2Cl2). 1H NMR (500 MHZ, DMSO): δ 1.33 (t, J=7.0 Hz, 3H), 1.50 (d, J=6.9 Hz, 3H), 4.38 (q, J=7.1 Hz, 2H), 5.24 (m, 1H), 7.05-7.45 (m, 5H), 7.87 (d, J=8.6 Hz, 1H), 7.94 (d, J=8.0 Hz, 1H), 8.2 (m, 1H), 8.44 (m, 1H), 8.91 (m, 1H), 9.14 (br s, 1H), 9.50 (s, 1H). Mass Spectrum (CH3CN-TFA-NH4HCO2-ESI): 455.2 (M+1).
Reaction SMILES: [C:1]([NH:3][C:4](=[N:7][CH:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11][CH2:10][CH2:9]1)SC)#[N:2].[CH2:18]([NH2:22])[CH2:19][CH2:20][CH3:21]>C(#N)C>[C:1]([N:3]=[C:4]([NH:7][CH:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11][CH2:10][CH2:9]1)[NH:22][CH2:18][CH2:19][CH2:20][CH3:21])#[N:2]
Reactant: CCCCN
Reactant: CSC(=NC1CCCc2ccccc21)NC#N
Solvent: CC#N
Product: CCCCNC(=NC#N)NC1CCCc2ccccc21
Reaction time: 100 h

Procedure:
A solution of 12.3 g of N-cyano-N'-(1,2,3,4-tetrahydro-1-naphthyl)-S-methylisothiourea and 20 ml of n-butylamine in 100 ml of acetonitrile was heated at reflux with stirring for 100 hours. The solvent was removed by evaporation in vacuo. The residual oil was dissolved in methylene chloride, and the solution was washed with three 80 ml portions of 3N hydrochloric acid and then dried over anhydrous sodium sulfate. The methylene chloride was removed by evaporation in vacuo, leaving as residue N"-cyano-N-n-butyl-N'-(1,2,3,4-tetrahydro-1-naphthyl)guanidine as 9.73 g of a pale yellow, viscous oil.
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH2:8]Br)=[CH:6][CH:5]=1)([O-:3])=[O:2].[NH:12]1[C:20]2[CH:19]=[CH:18][CH:17]=[C:16]([CH:21]=[O:22])[C:15]=2[CH:14]=[CH:13]1>>[N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH2:8][N:12]2[C:20]3[CH:19]=[CH:18][CH:17]=[C:16]([CH:21]=[O:22])[C:15]=3[CH:14]=[CH:13]2)=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: O=Cc1cccc2[nH]ccc12
Reactant: O=[N+]([O-])c1ccc(CBr)cc1
Product: O=Cc1cccc2c1ccn2Cc1ccc([N+](=O)[O-])cc1
Yield: 55.4 %

Procedure:
The same procedures used in Example 7 were repeated except for using 4.46 g of 4-nitrobenzyl bromide and 2.00 g of indole-4-carbaldehyde as a starting material to give 2.14 g of 1-(4-nitrobenzyl) indole-4-carbaldehyde as an orange-colored oily substance. The yield thereof was found to be 59%.
Reaction SMILES: [CH2:1]([N:4]1[C:8]([OH:9])=[C:7]([C:10](=[O:19])[C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=2[Cl:18])[C:6]([CH3:20])=[N:5]1)[CH:2]=[CH2:3].C1C=CC=CC=1.C(N(CC)CC)C.[C:34]1([CH3:44])[CH:39]=[CH:38][C:37]([S:40](Cl)(=[O:42])=[O:41])=[CH:36][CH:35]=1>O>[C:34]1([CH3:44])[CH:39]=[CH:38][C:37]([S:40]([O:9][C:8]2[N:4]([CH2:1][CH:2]=[CH2:3])[N:5]=[C:6]([CH3:20])[C:7]=2[C:10](=[O:19])[C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=2[Cl:18])(=[O:42])=[O:41])=[CH:36][CH:35]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: C=CCn1nc(C)c(C(=O)c2ccc(Cl)cc2Cl)c1O
Solvent: O
Solvent: CCN(CC)CC
Solvent: c1ccccc1
Product: C=CCn1nc(C)c(C(=O)c2ccc(Cl)cc2Cl)c1OS(=O)(=O)c1ccc(C)cc1

Procedure:
To a solution of 180 mg. of 1-allyl-3-methyl-4-(2,4-dichlorobenzoyl)-5-hydroxypyrazole in 6 ml. of benzene and 58.4 mg. of triethylamine is added dropwise 110 mg. of 4-toluenesulfonyl chloride with stirring at room temperature. Then, the resulting mixture is heated under reflux for 1 hour. After completion of the reaction, water is added to the reaction mixture and an organic layer is separated. The organic layer is dried over anhydrous sodium sulfate, the solvent is distilled off and the resulting oily substance is recrystallized from benzene-n-hexane to give 173 mg. of the desired product as colorless prisms melting at 113°-114° C. Further, the solvent is distilled off from the mother liquor and recrystallization from n-hexane gives 26 mg. of the desired product. Total yield 73.9%
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[CH:9]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:10][C:11]([OH:13])=O.[NH2:20][CH2:21][C:22]([NH:24][CH:25]1[CH:30]2[CH:26]1[CH2:27][N:28]([CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH2:29]2)=[O:23].C(OC(NCC(O)=O)=O)(C)(C)C.C(N1CC2C(C2N)C1)C1C=CC=CC=1.CN1CCOCC1.C1C=CC2N(O)N=NC=2C=1>CN(C)C=O.O>[CH2:31]([N:28]1[CH2:27][CH:26]2[CH:30]([CH:25]2[NH:24][C:22]([CH2:21][NH:20][C:11](=[O:13])[CH2:10][CH:9]([C:3]2[CH:4]=[C:5]([CH3:8])[CH:6]=[CH:7][C:2]=2[OH:1])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:23])[CH2:29]1)[C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1
Reactant: Cc1ccc(O)c(C(CC(=O)O)c2ccccc2)c1
Reactant: NCC(=O)NC1C2CN(Cc3ccccc3)CC21
Agent: CC(C)(C)OC(=O)NCC(=O)O
Agent: NC1C2CN(Cc3ccccc3)CC12
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CN1CCOCC1
Solvent: CN(C)C=O
Product: Cc1ccc(O)c(C(CC(=O)NCC(=O)NC2C3CN(Cc4ccccc4)CC32)c2ccccc2)c1
Reaction time: 1 h

Procedure:
The compound, 3-(2-hydroxy-5-methylphenyl)-3-phenyl propionic acid (198 mg, 0.77 mmole, 1 eq) and 2-amino-N-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl)-acetamide, 200 mg, 0.179 mmole, 1 eq prepared by reacting t-butoxy carbonylamino-acetic acid with 3-benzyl-3-azabicylo[3.1.0]hex-6-yl amine, which in turn, was prepared following the procedure of T. F. Braish et al., Synlett, 1996, 1100) were dissolved in dimethylformamide (3 ml). The reaction mixture was cooled to 0° C. with subsequent addition of N-methyl morpholine (2.31 mmole, 3 eq) and HOBT (0.77 mmole, 1 eq). The resulting reaction mixture was stirred for 1 hour at the same temperature and then at room temperature. The reaction mixture was diluted with water and extracted the organic compound with ethyl acetate. The solvent was removed under reduced pressure and dried. The crude compound was purified by column chromatography using ethyl acetate, methanol and dichloromethane solvent system.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([CH:14]2[CH2:16][CH2:15]2)=[CH:10][C:9]=1[NH:17][C:18](=[O:33])[CH2:19][C:20]([C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([N:28]2[CH:32]=[CH:31][N:30]=[CH:29]2)[CH:23]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:14]1([C:11]2[CH:12]=[CH:13][C:8]3[N:7]=[C:20]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([N:28]5[CH:32]=[CH:31][N:30]=[CH:29]5)[CH:23]=4)[CH2:19][C:18](=[O:33])[NH:17][C:9]=3[CH:10]=2)[CH2:16][CH2:15]1
Reactant: CC(C)(C)OC(=O)Nc1ccc(C2CC2)cc1NC(=O)CC(=O)c1cccc(-n2ccnc2)c1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C1CC(c2cccc(-n3ccnc3)c2)=Nc2ccc(C3CC3)cc2N1

Procedure:
Prepared from {4-cyclopropyl-2-[3-(3-imidazol-1-yl-phenyl)-3-oxo-propionylamino]-phenyl}-carbamic acid tert.-butyl ester (Example K80) by treatment with TFA in CH2Cl2 according to the general procedure M. Obtained as a light brown solid (41 mg).
Reaction SMILES: [Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=[C:6]2[N:5]=[C:4]([NH2:15])[CH:3]=1.[Cl-].[CH3:17][O:18][C:19](=[O:29])[C:20]1[CH:28]=[CH:27][C:23]([C:24](O)=[O:25])=[CH:22][CH:21]=1>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:11]([F:12])([F:13])[F:14])[CH:10]=[C:6]2[N:5]=[C:4]([NH:15][C:24]([C:23]2[CH:27]=[CH:28][C:20]([C:19]([O:18][CH3:17])=[O:29])=[CH:21][CH:22]=2)=[O:25])[CH:3]=1
Reactant: Nc1cc(Cl)n2nc(C(F)(F)F)cc2n1
Reactant: COC(=O)c1ccc(C(=O)O)cc1
Agent: CN(C)c1ccncc1
Agent: [Cl-]
Solvent: c1ccncc1
Product: COC(=O)c1ccc(C(=O)Nc2cc(Cl)n3nc(C(F)(F)F)cc3n2)cc1
Temperature: 0 °C
Reaction time: 48 h
Yield: 10 %

Procedure:
7-chloro-2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-5-amine (0.5 g, 1.0 equivalent) was suspended in pyridine (0.2 M) in a round bottom flask. At 0° C. was added a solution of terephthalic acid monomethylester chloride (2.0 equivalents) pre-dissolved in pyridine (0.8M), and followed by addition of N,N-dimethylpyridin-4-amine (0.1 equivalent). The mixture was stirred vigorously at 0° C. for 48 h. The reaction was quenched with saturated NaHCO3; pyridine was removed in vacuo and the residue was extracted with EtOAc twice and the combined organic layers were dried over Na2SO4. The organic layers were concentrated in vacuo and the crude mixture was purified using chromatography (SiO2, gradient of 10 to 50% EtOAc/hexanes) to afford the titled compound (10%) as a solid. Melting point (191.0-195.0° C.). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.90 (s, 3 H) 7.20 (s, 1 H) 8.06-8.11 (m, 2 H) 8.12-8.18 (m, 2 H) 8.32 (s, 1 H) 11.88 (s, 1 H); ESI-MS: m/z 399.0 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:9][C:10]([OH:12])=O)[CH:6]=[CH:7][CH:8]=1.[NH2:13][CH:14]([CH2:22][CH3:23])[C:15]([O:17][CH2:18][CH:19]([CH3:21])[CH3:20])=[O:16]>>[CH2:18]([O:17][C:15](=[O:16])[CH:14]([NH:13][C:10](=[O:12])[CH2:9][C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=1)[CH2:22][CH3:23])[CH:19]([CH3:20])[CH3:21]
Reactant: CCC(N)C(=O)OCC(C)C
Reactant: COc1cccc(CC(=O)O)c1
Product: CCC(NC(=O)Cc1cccc(OC)c1)C(=O)OCC(C)C

Procedure:
Following General Procedure BI above and using 3-methoxyphenylacetic acid (Aldrich) and iso-butyl 2-aminobutyrate (prepared frollowing General Procedure BJ above), the title compound was prepared. The reaction was monitored by tlc on silica gel and purification was by filtration as described in the general procedure.
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[C:7]2[S:9][C:10]3[CH2:15][CH2:14][CH2:13][CH2:12][C:11]=3[C:6]2=[C:5]([C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)[C:4]=1[CH2:23][C:24]([O:26][CH3:27])=[O:25].I[CH2:29][CH2:30][CH3:31]>>[CH3:1][O:2][C:3]1[N:8]=[C:7]2[S:9][C:10]3[CH2:15][CH2:14][CH2:13][CH2:12][C:11]=3[C:6]2=[C:5]([C:16]2[CH:17]=[CH:18][C:19]([CH3:22])=[CH:20][CH:21]=2)[C:4]=1[CH:23]([CH2:29][CH2:30][CH3:31])[C:24]([O:26][CH3:27])=[O:25]
Reactant: CCCI
Reactant: COC(=O)Cc1c(OC)nc2sc3c(c2c1-c1ccc(C)cc1)CCCC3
Product: CCCC(C(=O)OC)c1c(OC)nc2sc3c(c2c1-c1ccc(C)cc1)CCCC3

Procedure:
The compound is prepared from the methyl [2-methoxy-4-(p-tolyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetate and 1-iodopropane as described in the general method C.
Reaction SMILES: C([N:5]1[CH:9](O)[C:8]2[CH:11]=[CH:12][CH:13]=[C:14]([Cl:15])[C:7]=2[S:6]1(=[O:17])=[O:16])(C)(C)C.CC1C=CC(S(O)(=O)=O)=CC=1.O>C1C=CC=CC=1>[Cl:15][C:14]1[C:7]2[S:6](=[O:17])(=[O:16])[N:5]=[CH:9][C:8]=2[CH:11]=[CH:12][CH:13]=1
Reactant: CC(C)(C)N1C(O)c2cccc(Cl)c2S1(=O)=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccccc1
Solvent: O
Product: O=S1(=O)N=Cc2cccc(Cl)c21
Reaction time: 16 h
Yield: 69.9 %

Procedure:
A solution of 37 g of 2-t-butyl-3-hydroxy-7-chloro-2,3-dihydro-1,2-benzoisothiazole-1,1-dioxide and 0.2 g of tosic acid in 370 mls of benzene was refluxed through a Dean-Stark water separator for 16 hours, cooled in ice and filtered to give 18.9 g of the title compound as colorless crystals, m.p. 162°-164° C.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=[O:12])[NH:4][N:3]=1.[C:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)#[CH:14].C(N(CC)CC)C>CN(C=O)C.CCOC(C)=O.[Cu]I.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>[C:15]1([C:13]#[C:14][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5](=[O:12])[NH:4][N:3]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: C#Cc1ccccc1
Reactant: O=c1[nH]nc(Cl)c2ccccc12
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: O=c1[nH]nc(C#Cc2ccccc2)c2ccccc12

Procedure:
A mixture of 4-chlorophthalazin-1(2H)-one, ethynylbenzene, triethylamine, copper(I) iodide, and Pd(PPh3)4 in DMF was microwaved at 185° C. for 30 minutes, diluted with EtOAc, washed with water and saturated aqueous NH4Cl, and chromatographed to give impure 4-(phenylethynyl)phthalazin-1(2H)-one, which was used without further purification. This material was treated with O-(diphenylphosphoryl)hydroxylamine as in Example 1B to give impure 2-amino-4-(phenylethynyl)phthalazin-1(2H)-one.
Reaction SMILES: C(OC([N:8]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH:23]2[CH2:28][CH2:27][N:26]([C:29]([C:31]3[CH:32]=[N:33][C:34]4[C:39]([CH:40]=3)=[CH:38][C:37]([Cl:41])=[CH:36][CH:35]=4)=[O:30])[CH2:25][CH2:24]2)[CH:18]=1)C(OC(C)(C)C)=O)=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[Cl:41][C:37]1[CH:38]=[C:39]2[C:34](=[CH:35][CH:36]=1)[N:33]=[CH:32][C:31]([C:29]([N:26]1[CH2:27][CH2:28][CH:23]([C:19]3[CH:18]=[C:17]([CH:22]=[CH:21][CH:20]=3)[CH2:16][NH2:8])[CH2:24][CH2:25]1)=[O:30])=[CH:40]2
Reactant: CC(C)(C)OC(=O)N(Cc1cccc(C2CCN(C(=O)c3cnc4ccc(Cl)cc4c3)CC2)c1)C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: NCc1cccc(C2CCN(C(=O)c3cnc4ccc(Cl)cc4c3)CC2)c1
Temperature: 25 °C
Yield: 91.6 %

Procedure:
N,N-bis-(tert-butoxycarbonyl)-3-[1-(6-Chloroquinoline-3-carbonyl)-piperidin-4-yl]benzylamine (0.055 g, 0.095 mmol) was treated with a solution of 15% trifluoroacetic acid in methylene chloride (5 ml) at 0° C. The reaction was warmed to ambient temperature over 2.5 hr and the solvents were removed in vacuo. The residue was triturated with ether to yield the title compound (0.033 g, 0.087 mmol) as an amorphous solid. 1H NMR[(CD3)2SO, 500 MHz]: δ 8.95 (s, 1H), 8.44 (s, 1H), 8.20 (s, 1H), 8.07 (d, 1H), 7.84 (d, 2H), 7.23-7.40 (m, 4H), 4.67 (m, 1H), 7.34 (m, 3H), 4.75 (br m, 1H), 4.05 (m, 2H), 3.75 (br m, 1H), 3.30 (br m, 1H), 2.80-3.00 (br m, 2H), 1.90 (br m, 1H), 1.6-1.8 (br m, 3H). MS(EI): 380(M++H).
Reaction SMILES: [CH3:1][C:2]([CH3:16])([O:4][C:5]([NH:7][C@H:8]([C:13]([OH:15])=[O:14])[CH2:9][CH:10]([CH3:12])[CH3:11])=[O:6])[CH3:3].[Cl:17][C:18]1[CH:23]=[C:22]([Cl:24])[C:21]([Cl:25])=[CH:20][C:19]=1O.C1(N=C=NC2CCCCC2)CCCCC1>C(OCC)(=O)C>[Cl:17][C:18]1[CH:23]=[C:22]([Cl:24])[C:21]([Cl:25])=[CH:20][C:19]=1[O:14][C:13](=[O:15])[C@H:8]([CH2:9][CH:10]([CH3:12])[CH3:11])[NH:7][C:5]([O:4][C:2]([CH3:3])([CH3:1])[CH3:16])=[O:6]
Reactant: CC(C)C[C@H](NC(=O)OC(C)(C)C)C(=O)O
Reactant: Oc1cc(Cl)c(Cl)cc1Cl
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CCOC(C)=O
Product: CC(C)C[C@H](NC(=O)OC(C)(C)C)C(=O)Oc1cc(Cl)c(Cl)cc1Cl
Yield: 100.6 %

Procedure:
N-(1,1-Dimethylethoxycarbonyl)leucine (6.32 g, 15 mmol) was stirred with 2,4,5-trichlorophenol (3.01 g, 15.2 mmol) and dicyclohexylcarbodiimide (3.14 g, 15.2 mmol) in ethyl acetate (50 mL) at -10° C. for 4 h. The suspension was filtered and the solvent was evaporated under reduced pressure from the filtrate. The residue was dissolved in ethyl acetate. The suspension was filtered and the solvent was evaporated under reduced pressure from the filtrate to give N-(1,1-dimethylethoxycarbonyl)leucine 2,4,5-trichlorophenyl ester (6.2 g, 99%).
Reaction SMILES: C(OC(=O)C)(=[O:3])C.[Mn]([O-])(=O)(=O)=O.[K+].[CH:14]([NH:16][C:17]1[S:18][CH:19]=[C:20]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[N:21]=1)=[O:15]>C(O)(=O)C>[CH:14]([NH:16][C:17]1[S:18][CH:19]=[C:20]([C:22](=[O:3])[C:23]([O:25][CH2:26][CH3:27])=[O:24])[N:21]=1)=[O:15]
Reactant: CC(=O)OC(C)=O
Reactant: CCOC(=O)Cc1csc(NC=O)n1
Agent: O=[Mn](=O)(=O)[O-]
Agent: CCOC(=O)Cc1csc(=NC=O)[nH]1
Agent: [K+]
Solvent: CC(=O)O
Product: CCOC(=O)C(=O)c1csc(NC=O)n1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
(b)-(ii) A mixture of manganous acetate tetrahydrate (120 g.), acetic acid (1000 ml.) and acetic anhydride (100 ml.) was stirred for 20 minutes in an oil bath heated at 130° to 135° C., and to the mixture was added potassium permanganate (20 g.) over 5 minutes at 105° to 110° C. with stirring and then the mixture was further stirred for 30 minutes at 130° to 135° C. The mixture was cooled to room temperature, and to the mixture was added ethyl 2-(2-formylamino-1,3-thiazol-4-yl)acetate, which can be represented as ethyl 2-(2-formylimino-2,3-dihydro-1,3-thiazol-4-yl)acetate, (53.5 g.), and then the mixture was stirred for 15 hours at 38° to 40° C. under introduction of air at the rate of 6000 ml. per minute. After the reaction, the precipitates were collected by filtration. The precipitates were washed with acetic acid and water in turn and then dried to give ethyl 2-(2-formylamino-1,3-thiazol-4-yl)glyoxylate, which can be represented as ethyl 2-(2-formylimino-2,3-dihydro-1,3-thiazol-4-yl)glyoxylate, (41.5 g.), mp 232° to 233° C. (dec.).
Reaction SMILES: [C:1]1(=[O:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:8]1(=O)[O:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1.[C:16]([O-])(=O)C=C>C(C(C)=O)C>[CH2:4]1[CH2:5][CH2:6][C:1]([OH:7])([C:13]([C:12]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:16]=2)=[O:14])[CH2:2][CH2:3]1
Reactant: O=C1CCCCCO1
Reactant: O=C1CCCCC1
Reactant: C=CC(=O)[O-]
Solvent: CCC(C)=O
Product: O=C(c1ccccc1)C1(O)CCCCC1

Procedure:
To 900 parts by weight of methyl ethyl ketone were added 100 parts by weight of cyclohexanone, 750 parts by weight of partially caprolactone-modified polyfunctional acrylate (DPCA-20, produced by Nippon Kayaku Co., Ltd.), 200 parts by weight of a silica sol (MIBK-ST, produced by Nissan Chemical Industries, Ltd.) and 50 parts by weight of a photopolymerization initiator (IRGACURE 184, produced by Ciba Specialty Chemicals Corp.), followed by stirring. The mixture was filtered through a polypropylene filter having a pore size of 0.4 μm to prepare Coating solution A for hardcoat layer.