Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:5]=[C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:3]=1.[N-:20]=[N+:21]=[N-:22].[Na+].[N-]=[N+]=[N-].[Li+]>C(#N)C>[N:20]([C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:5]=[C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:3]=1)=[N+:21]=[N-:22]
Reactant: [N-]=[N+]=[N-]
Reactant: Clc1nc(-c2ccccc2)nc(-c2ccccc2)n1
Agent: [Li+]
Agent: [Na+]
Solvent: CC#N
Product: [N-]=[N+]=Nc1nc(-c2ccccc2)nc(-c2ccccc2)n1
Temperature: 25 °C
Reaction time: 264 h
Yield: 22.5 %

Procedure:
A suspension of 2-chloro-4,6-diphenyl-s-triazine (30 g, 0.112 mol), sodium azide (12.86 g, 0.199 mol) and lithium azide (1.25 g, 0.025 mol) in acetonitrile (550 ml) was stirred at room temperature for 11 days. After filtration, the filtrate on evaporation yielded 6.9 g of 2-azido-4,6-diphenyl-s-triazine, mp 115°-117° C. The residue on extraction with hot heptane, followed by crystallization from heptane, gave an additional 20 g quantity having a mp of 114°-116° C. bringing the total yield of 2-azido-4,6-diphenyl-s-triazine to 26.9 g (88% yield). The melting point and infrared spectrum were identical with that of an authentic sample.
Reaction SMILES: [C:1]1(=[O:8])[O:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CCCCC(C([O-])=[O:17])CC.CCCCC(C([O-])=O)CC.[Sn+2]>>[OH:17][CH:2]([CH2:3][CH2:4][CH2:5][CH:6]=[O:7])[CH:1]=[O:8]
Reactant: O=C1CCCCCO1
Reactant: CCCCC(CC)C(=O)[O-]
Agent: [Sn+2]
Product: O=CCCCC(O)C=O

Procedure:
2-Hydroxyadipaldehyde (Aldrich) was reacted with amino terminated PEG to form the Schiff base which was hydrogenated with NaBH4 to form the corresponding amine. The di-PEG derivative was reacted with lactide or caprolactone in the presence of stannous octoate to form the PLA or PCL-PEG2 diblock copolymer.
Reaction SMILES: [CH3:1][C:2]1([CH3:12])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4][CH2:3]1.C1C[O:16][CH2:15][CH2:14]1.C(OCC)(=[O:20])C>C([O-])(O)=O.[Na+]>[OH:20][CH:5]1[C:6]2[C:11](=[CH:10][C:9]([C:15](=[O:16])[CH3:14])=[CH:8][CH:7]=2)[C:2]([CH3:12])([CH3:1])[CH2:3][CH2:4]1
Reactant: CCOC(C)=O
Reactant: CC1(C)CCCc2ccccc21
Reactant: C1CCOC1
Agent: O=C([O-])O
Agent: [Na+]
Product: CC(=O)c1ccc2c(c1)C(C)(C)CCC2O
Temperature: 25 °C

Procedure:
A solution of 1-hydroxy-6-(1,3-dioxolan-2-yl)]-1,2,3,4-tetrahydro-4,4-dimethylnaphthalene (Compound D24, 54.9 mg, 0.21 mmol) in 3 ml of 10% HCa and 3 ml THF was heated at 100° C. for 1.5 h and cooled to room temperature. The reaction mixture was diluted with ethyl acetate and neutralized with sat. NaHCO3. The organic layer was further washed with brine, dried and concentrated to an oil. Purification by column chromatography (silica) with ethyl acetate/hexane (1/9) gave the title compound as a clear oil (24.8 mg).
Reaction SMILES: C1(S(O[C:11]2[CH:16]=[C:15]([CH3:17])[CH:14]=[C:13]([CH3:18])[CH:12]=2)(=O)=O)C=CC=CC=1.[NH2:19][C:20]1[CH:28]=[CH:27][C:23]([C:24]([NH2:26])=[O:25])=[CH:22][CH:21]=1>C(OCC)(=O)C>[CH3:17][C:15]1[CH:16]=[C:11]([NH:19][C:20]2[CH:28]=[CH:27][C:23]([C:24]([NH2:26])=[O:25])=[CH:22][CH:21]=2)[CH:12]=[C:13]([CH3:18])[CH:14]=1
Reactant: NC(=O)c1ccc(N)cc1
Reactant: Cc1cc(C)cc(OS(=O)(=O)c2ccccc2)c1
Solvent: CCOC(C)=O
Product: Cc1cc(C)cc(Nc2ccc(C(N)=O)cc2)c1
Yield: 95.7 %

Procedure:
Following the general procedure, 3,5-dimethylphenyl benzenesulfonate (131 mg, 0.5 mmol) was coupled with 4-aminobenzamide (102 mg, 0.75 mmol) with the reaction time of 6 h. Chromatography on silica gel column with ethyl acetate gave 115 mg (96%) of the title compound as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=O)[CH2:10][C:11]#[N:12])=[CH:5][CH:4]=1.O.[NH2:15][NH2:16]>C(O)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[C:11]([NH2:12])[NH:16][N:15]=2)=[CH:5][CH:4]=1
Reactant: COc1ccc(C(=O)CC#N)cc1
Reactant: NN
Solvent: CCO
Solvent: O
Product: COc1ccc(-c2cc(N)[nH]n2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 3-(4-methoxyphenyl)-3-oxopropanenitrile (5.0 g, 28.5 mmol) in ethanol (100 mL) was added hydrazine hydrate (2.8 mL, 57.1 mmol) at room temperature. The mixture was heated to reflux for 8 h, allowed to cool and concentrated under reduced pressure to about ¼ volume (25 mL). The resulting precipitate was allowed to stir overnight at room temperature, filtered and rinsed with ethanol (2 mL). The title product was dried under vacuum. Yield 4.15 g (77%); LCMS m/z 190.1 (M+H)+, ret. time=1.56 min.
Reaction SMILES: [C:1]([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][C:34]([OH:36])=O)(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].C(Cl)(=O)C([Cl:40])=O>O1CCCC1>[C:1]([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][C:34]([Cl:40])=[O:36])(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: O=C(Cl)C(=O)Cl
Reactant: CCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC(=O)O
Solvent: C1CCOC1
Product: CCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC(=O)Cl
Temperature: 25 °C
Reaction time: 72 h
Yield: 99.9 %

Procedure:
16-Hexadecanoyloxyhexadecanoic acid (7.73 g, 15.13 mmol) prepared as in (c) above was dissolved in tetrahydrofuran (140 ml) and oxalyl chloride (4.80 g, 37.83 mmol) was added dropwise. The mixture was stirred at room temperature for 3 days and then the solvent and unreacted oxalyl chloride were evaporated under reduced pressure to give 8.0 g (100%) of the title compound.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2N)[CH:4]=[N:3]1.N([O-])=O.[Na+].[ClH:18].[S:19](=[O:21])=[O:20]>C(O)(=O)C.O>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[S:19]([Cl:18])(=[O:21])=[O:20])[CH:4]=[N:3]1
Reactant: Cn1cc(-c2ccccc2N)cn1
Reactant: Cl
Reactant: O=S=O
Agent: O=N[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: Cn1cc(-c2ccccc2S(=O)(=O)Cl)cn1

Procedure:
By the procedure of Example 4, 17.3 g of 1-methyl-4-(2-aminophenyl)-1H-pyrazole prepared in Example 18 was diazotized with 7.2 g of sodium nitrite and 36 ml of concentrated HCl in 104 ml of glacial acetic acid. The diazonium salt suspension was added to a suspension containing 4.3 g of cupric chloride dihydrate, 30 ml of sulfur dioxide and 76 ml of acetic acid. After completion of the reaction and addition of water, the suspension was extracted with 1-chlorobutane. The extraction was dried over sodium sulfate and concentrated in vacuo at less than 40° C. to yield 22 g of crude 2-(1-methyl-1H-pyrazol-4-yl)benzenesulfonyl chloride as an oil.
Reaction SMILES: C(O[CH2:4][CH3:5])C.C[Li].C1(C2([C:19]3[C:31]4[CH2:30][C:29]5[C:24](=[CH:25][CH:26]=[C:27]([C:32]([CH3:35])([CH3:34])[CH3:33])[CH:28]=5)[C:23]=4[CH:22]=[CH:21][C:20]=3[C:36]([CH3:39])([CH3:38])[CH3:37])CCCCC2)C=CC=C1.[Cl-:40].[Cl-].[Cl-].[Cl-].[Zr+4:44]>ClCCl.C1COCC1>[Cl-:40].[Cl-:40].[C:19]1(=[Zr+2:44]([CH:5]2[CH:4]=[CH:29][CH:24]=[CH:25]2)[C:19]2[C:31]3[CH2:30][C:25]4[C:24](=[CH:29][CH:28]=[C:27]([C:32]([CH3:33])([CH3:34])[CH3:35])[CH:26]=4)[C:23]=3[CH:22]=[CH:21][C:20]=2[C:36]([CH3:38])([CH3:37])[CH3:39])[CH2:31][CH2:23][CH2:22][CH2:21][CH2:20]1
Reactant: CC(C)(C)c1ccc2c(c1)Cc1c-2ccc(C(C)(C)C)c1C1(C2C=CC=C2)CCCCC1
Reactant: CCOCC
Reactant: [Zr+4]
Agent: [Cl-]
Agent: [Li]C
Solvent: ClCCl
Solvent: C1CCOC1
Product: CC(C)(C)c1ccc2c(c1)Cc1c-2ccc(C(C)(C)C)c1[Zr+2](=C1CCCCC1)C1C=CC=C1
Temperature: 25 °C
Reaction time: 7 h

Procedure:
5.8 ml (5.8 mmol) of a diethyl ether solution of methyllithium were added dropwise under ice cooling under nitrogen to a THF (20 ml) solution including 1.0 g (2.36 mmol) of 1-cyclopentadienyl-1-(2,7-di-tert-butylfluorenyl)cyclohexane synthesized in the above-mentioned (2), followed by stirring at room temperature for 7 hours. Next, the THF was distilled off under nitrogen, and the resultant solid was washed with hexane and then dissolved in dichloromethane cooled to −78° C. To this solution, zirconium tetrachloride 2THF complex (0.81 g, 2.15 mmol) dissolved in dichloromethane was added at −78° C., and after stirring for 24, the temperature of the solution was slowly returned to room temperature.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Br)(Br)(Br)[Br:15].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][Br:15])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: BrC(Br)(Br)Br
Reactant: OCCCCCCc1ccccc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: BrCCCCCCc1ccccc1
Temperature: 0 °C
Reaction time: 2.5 h

Procedure:
A solution of 6-phenylhexanoic acid (19.8 mmol) in sieve dried tetrahydrofuran (5 ml) was reduced with diborane in tetrahydrofuran (30 ml, 29.1 mmol) at 0° C. for 4 hours to give 6-phenylhexanol. To an ice cold solution of the hexanol (ca. 19.8 mmol) and carbon tetrabromide (21.98 mmol) in methylene chloride (50 ml) was added triphenylphosphine (22-30 mmol) in methylene chloride (50 ml) and the resulting solution was stirred for 2.5 hours. The volatiles were evaporated and the residue was taken up in ether (100 ml), cooled in ice, and filtered. The filtrate was evaporated and distilled to afford 6-phenylhexyl bromide as an oil. A mixture of the bromide (8.00 mmol), salicylaldehyde (8.19 mmol) and potassium carbonate (9.33 mmol) in dimethylformamide (10 ml) was heated to 100° C. and maintained at that temperature for one hour. The cooled reaction mixture was taken up in hexane (50 ml) and washed with 5% sodium hydroxide (50 ml) and saturated sodium chloride (50 ml). The organic phase was dried over anhydrous magnesium sulfate and charcoal. Evaporated yielded a colorless oil which was purified by flash chromatography over silica gel with 5% ethyl acetate in hexane as eluant to afford the desired product as an oil.
Reaction SMILES: [F:1][C:2]1([F:45])[CH2:7][C@H:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([S:15]([N:18](CC3C=CC(OC)=CC=3OC)[C:19]3[CH:24]=[CH:23][N:22]=[CH:21][N:20]=3)(=[O:17])=[O:16])=[C:11]([F:36])[CH:10]=2)[C@@H:5]([C:37]2[CH:38]=[N:39][N:40](COC)[CH:41]=2)[CH2:4][CH2:3]1.C([SiH](CC)CC)C>ClCCl.FC(F)(F)C(O)=O>[F:45][C:2]1([F:1])[CH2:7][C@H:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([S:15]([NH:18][C:19]3[CH:24]=[CH:23][N:22]=[CH:21][N:20]=3)(=[O:16])=[O:17])=[C:11]([F:36])[CH:10]=2)[C@@H:5]([C:37]2[CH:41]=[N:40][NH:39][CH:38]=2)[CH2:4][CH2:3]1
Reactant: COCn1cc([C@H]2CCC(F)(F)C[C@@H]2Oc2ccc(S(=O)(=O)N(Cc3ccc(OC)cc3OC)c3ccncn3)c(F)c2)cn1
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=S(=O)(Nc1ccncn1)c1ccc(O[C@H]2CC(F)(F)CC[C@@H]2c2cn[nH]c2)cc1F
Reaction time: 2 h
Yield: 46.4 %

Procedure:
To a solution of the 4-({(1S*,2R*)-5,5-difluoro-2-[1-(methoxymethyl)-1H-pyrazol-4-yl]cyclohexyl}oxy)-N-(2,4-dimethoxybenzyl)-2-fluoro-N-(pyrimidin-4-yl)benzenesulfonamide (0.12 g, 0.19 mmol) prepared in Example 147d and triethylsilane (0.15 mL) in dichloromethane (4.0 mL), trifluoroacetic acid (3.0 mL) was added at room temperature, and the reaction solution was stirred for 2 hours. The reaction solution was concentrated, then ethanol (1.0 mL) and 2 M hydrochloric acid (4.0 mL) were added to the residue, and the mixture was stirred at 100° C. for 3 hours. After allowing to cool, the reaction solution was neutralized with sodium hydrogencarbonate, and the resulting solid was collected by filtration. The solid thus collected by filtration was purified with silica gel chromatography (dichloromethane/methanol=95:5) to yield the title compound (40 mg, 48%) as a colorless solid.
Reaction SMILES: [CH2:1]([O:3][CH:4]([O:13][CH2:14][CH3:15])[C:5]1[CH:12]=[CH:11][C:8]([CH:9]=O)=[CH:7][CH:6]=1)[CH3:2].[CH3:16][Si:17]([CH3:30])([CH3:29])[CH2:18][CH2:19][O:20][CH2:21][N:22]1[CH:26]=[CH:25][N:24]=[C:23]1[CH2:27][NH2:28]>>[CH2:1]([O:3][CH:4]([O:13][CH2:14][CH3:15])[C:5]1[CH:12]=[CH:11][C:8]([CH2:9][NH:28][CH2:27][C:23]2[N:22]([CH2:21][O:20][CH2:19][CH2:18][Si:17]([CH3:30])([CH3:29])[CH3:16])[CH:26]=[CH:25][N:24]=2)=[CH:7][CH:6]=1)[CH3:2]
Reactant: C[Si](C)(C)CCOCn1ccnc1CN
Reactant: CCOC(OCC)c1ccc(C=O)cc1
Product: CCOC(OCC)c1ccc(CNCc2nccn2COCC[Si](C)(C)C)cc1
Yield: 106.3 %

Procedure:
With 4-(diethoxymethy)benzaldehyde (957 mg) and 1-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)methanamine (1.05 g), the same operation as in Example 2 was performed to obtain the title compound (2.05 g) having the following physical properties.
Reaction SMILES: [C:1]([C@@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[C:9]1[N:14]=[C:13]([Cl:15])[N:12]=[C:11]([C:16]([O:18]C)=O)[CH:10]=1)(=[O:3])[NH2:2].[NH3:20]>CO>[C:1]([C@@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[C:9]1[N:14]=[C:13]([Cl:15])[N:12]=[C:11]([C:16]([NH2:20])=[O:18])[CH:10]=1)(=[O:3])[NH2:2]
Reactant: N
Reactant: COC(=O)c1cc(N2CCC[C@H]2C(N)=O)nc(Cl)n1
Solvent: CO
Product: NC(=O)c1cc(N2CCC[C@H]2C(N)=O)nc(Cl)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 76 %

Procedure:
A mixture of (S)-methyl 6-(2-carbamoylpyrrolidin-1-yl)-2-chloropyrimidine-4-carboxylate (0.849 g, 2.98 mmol) in 7M ammonia in MeOH (5.0 mL) was stirred at ambient temperature overnight and then filtered. The filter cake was washed with methanol (1×2 mL)) and dried under vacuum at 40° C. to give (S)-6-(2-carbamoylpyrrolidin-1-yl)-2-chloropyrimidine-4-carboxamide as a white powder (0.611 g, 2.27 mmol, 76% yield). LC/MS: m/z=270.2 [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([F:21])[C:5]([F:20])=[C:6]([C@:8]2([CH3:19])[CH2:13][C@@H:12]([C:14]([F:17])([F:16])[F:15])[O:11][C:10]([NH2:18])=[N:9]2)[CH:7]=1.[Cl:22][C:23]1[CH:24]=[N:25][C:26]2[C:31]([CH:32]=1)=[CH:30][CH:29]=[N:28][C:27]=2Cl>>[Cl:22][C:23]1[CH:24]=[N:25][C:26]2[C:31]([CH:32]=1)=[CH:30][CH:29]=[N:28][C:27]=2[NH:1][C:2]1[CH:3]=[C:4]([F:21])[C:5]([F:20])=[C:6]([C@:8]2([CH3:19])[CH2:13][C@@H:12]([C:14]([F:17])([F:16])[F:15])[O:11][C:10]([NH2:18])=[N:9]2)[CH:7]=1
Reactant: C[C@@]1(c2cc(N)cc(F)c2F)C[C@@H](C(F)(F)F)OC(N)=N1
Reactant: Clc1cnc2c(Cl)nccc2c1
Product: C[C@@]1(c2cc(Nc3nccc4cc(Cl)cnc34)cc(F)c2F)C[C@@H](C(F)(F)F)OC(N)=N1

Procedure:
The titled compound was synthesized by procedure and steps analogous to those described in Method B, Step 2, Example 8 above, but using (4S,6S)-4-(5-amino-2,3-difluorophenyl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (17i, Example 163, Method Y step 9) in step 2 and 3,8-dichloro-1,7-naphthyridine (intermediate 2). MS m/z=472.1 [M+H]+. Calculated for C20H15ClF5N50: 471.8
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[F:11][C:12]1[CH:19]=[CH:18][C:15]([CH:16]=[O:17])=[CH:14][CH:13]=1.FC(F)(F)S(O[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[Si](C)(C)C)(=O)=O.[F-].[K+].C1OCCOCCOCCOCCOCCOC1>C1COCC1>[F:11][C:12]1[CH:19]=[CH:18][C:15]([CH:16]2[O:17][CH:2]3[CH:3]=[CH:4][C:5]4[C:10]([N:1]3[C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][C:26]2=3)=[CH:9][CH:8]=[CH:7][CH:6]=4)=[CH:14][CH:13]=1
Reactant: c1ccc2ncccc2c1
Reactant: C[Si](C)(C)c1ccccc1OS(=O)(=O)C(F)(F)F
Reactant: O=Cc1ccc(F)cc1
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [F-]
Agent: [K+]
Solvent: C1CCOC1
Product: Fc1ccc(C2OC3C=Cc4ccccc4N3c3ccccc32)cc1
Yield: 96 %

Procedure:
Following the general procedure, treatment of quinoline (0.064 g, 59 μL, 0.50 mmol) and 4-fluorobenzaldehyde (0.093 g, 80 μL, 0.75 mmol) with 2-(trimethylsilyl)phenyl trifluoromethanesulfonate (0.179 g, 146 μL, 0.60 mmol) in the presence of KF (0.070 g, 1.2 mmol) and 18-crown-6 (0.317 g, 1.2 mmol) in THF (2.0 mL) at 10° C. to room temperature for 12 hrs followed by flash column chromatography (Pet. ether/EtOAc=75/25) of the crude reaction mixture afforded 5-(4-fluorophenyl)-5H,6aH-benzo[4,5][1,3]oxazino[3,2-a]quinoline as inseparable mixture of diastereomers as a yellow solid (0.158 g, 96% yield, dr determined by 1H NMR analysis of crude reaction mixture is >20:1).
Reaction SMILES: [NH:1]([C:8]1[C:9](=[O:20])[C:10](=[N:13][C:14]2[CH:19]=CC=C[CH:15]=2)[C:11]=1[OH:12])[C:2]1[CH:7]=CC=C[CH:3]=1.C[C@H]1N[C@@H:26]([CH3:28])[CH2:25][N:24]([CH2:29][CH2:30][CH3:31])C1>>[OH-:12].[OH:12][C:11]1[C:10](=[N+:13]2[C@H:14]([CH3:15])[CH2:19][N:24]([CH2:25][CH2:26][CH3:28])[CH2:29][C@@H:30]2[CH3:31])[C:9](=[O:20])[C:8]=1[N:1]1[C@H:2]([CH3:3])[CH2:7][N:24]([CH2:29][CH2:30][CH3:31])[CH2:25][C@@H:26]1[CH3:28]
Reactant: CCCN1C[C@@H](C)N[C@@H](C)C1
Reactant: O=c1c(Nc2ccccc2)c(O)c1=Nc1ccccc1
Product: CCCN1C[C@@H](C)N(c2c(O)c(=[N+]3[C@H](C)CN(CCC)C[C@@H]3C)c2=O)[C@@H](C)C1
Product: [OH-]

Procedure:
A mixture of 0.48 grams of 2-anilino-3-hydroxy-4-(phenylimino)-2-cyclobuten-1-one and 0.63 grams of cis-3,5-dimethyl-1-propylpiperazine is heated at 230°-240° C. for 10 minutes. The product is then isolated from the reaction mixture according to the procedure described in Example 5 to give 1-[2-hydroxy-3-(cis-2,6-dimethyl-4-propyl-1-piperazinyl)-4-oxo-2-cyclobuten-1-ylidene]-cis-2,6-dimethyl-4-propylpiperazinium hydroxide inner salt melting at about 218°-227° C. This compound has the following formula ##STR3##
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:26])[NH:10][C@@H:11]([CH3:25])[CH:12]([O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])[CH2:13][CH2:14][CH2:15]O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.O>O1CCCC1>[Si:18]([O:17][CH:12]1[CH2:13][CH2:14][CH2:15][N:10]([C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:26])[C@H:11]1[CH3:25])([C:21]([CH3:23])([CH3:22])[CH3:24])([CH3:19])[CH3:20]
Reactant: C[C@H](NC(=O)OCc1ccccc1)C(CCCO)O[Si](C)(C)C(C)(C)C
Agent: CS(=O)(=O)Cl
Solvent: O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: C[C@H]1C(O[Si](C)(C)C(C)(C)C)CCCN1C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 30 h
Yield: 63.5 %

Procedure:
To a solution (15 mL) of benzyl((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-5-hydroxy-1-methylpentyl)carbamate (430 mg) in tetrahydrofuran were added triethylamine (0.235 mL) and methanesulfonyl chloride (0.105 mL) under ice-cooling, and the mixture was stirred at room temperature for 30 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (20 mL). Potassium tert-butoxide (152 mg) was added under ice-cooling, and the mixture was stirred at room temperature for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with 0.1N hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (developing solvent: hexane:ethyl acetate=9:1→2:1) to give the title compound (yield: 260 mg) as a colorless oil.
Reaction SMILES: CS(Cl)(=O)=O.[CH3:6][O:7][C:8]1[CH:9]=[CH:10][C:11]2[S:15][C:14]([CH2:16][C:17]3(O)C4C[CH:20]5[CH2:21][CH:22](C[CH:18]3[CH2:19]5)[CH2:23]4)=[N:13][C:12]=2[CH:28]=1.C(N(CC)CC)C>ClCCl.C(OCC)(=O)C>[CH2:18]1[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:17]1=[CH:16][C:14]1[S:15][C:11]2[CH:10]=[CH:9][C:8]([O:7][CH3:6])=[CH:28][C:12]=2[N:13]=1
Reactant: COc1ccc2sc(CC3(O)C4CC5CC(C4)CC3C5)nc2c1
Agent: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: COc1ccc2sc(C=C3CCCCCC3)nc2c1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
187 μl of methanesulfonyl chloride are added to a mixture of 350 mg of 2-(5-methoxybenzothiazol-2-ylmethyl)cycloheptan-2-ol (formula IX), 665 μl of triethylamine and a catalytical amount of 4-N,N-dimethylaminopyridine in 12 ml of dry dichloromethane at about 0°. The mixture is stirred for about 12 hours at room temperature, 187 μl of methansulfonyl chloride and 665 μl of triethylamine are added and the resultant reaction mixture is stirred at about 40° for about 48 hours. The mixture is diluted with 100 ml of ethyl acetate and then extracted with 1 M aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution and brine. The organic phase is dried and the solvent is evaporated off. The residue is subjected to chromatography. The title compound is obtained [13C-NMR (125.8 MHz): 166.528, 158.978, 155.645, 154.597, 126.878, 121.337, 119.750, 114.743, 105.127, 55.561, 39.394, 33.143, 29.921, 29.344, 28.775, 26.435],
Reaction SMILES: C[O:2][C:3](OC)([C:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:11])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(O)COCCOCCO.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>>[C:12]1([C:10]([C:3]([C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)=[O:2])=[O:11])[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: COC(OC)(C(=O)c1ccccc1)c1ccccc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: OCCOCCOCCO
Solvent: O
Product: O=C(C(=O)c1ccccc1)c1ccccc1
Temperature: 80 °C

Procedure:
A mixture of 153.8 g (0.6 mole) of benzil dimethyl ketal, 90.1 g (0.6 mole) of triethylene glycol and 3.9 g of toluene-4-sulfonic acid monohydrate are heated to 75-85° C. under an aspirator vacuum (20-30 mbar). At about 63° C., everything is dissolved. The course of the reaction is monitored by thin-layer chromatography. The reaction is stopped as soon as less than 1% of benzil dimethyl ketal is present in the mixture or the amount of benzil formed is larger than the amount of benzil dimethyl ketal still present. This is the case after 2-3 hours. The yellow solution is then cooled and neutralized with 3.8 g of a 30% solution of sodium methylate in methanol. The mixture is then heated to 60° C. under an aspirator vacuum and the methanol is distilled off. The liquid residue is diluted with 500 ml of toluene, stirred with 10 g of activated carbon and filtered through a Hyflo bed. The filtrate is evaporated in vacuo. This gives 208.8 g of a yellow, viscous oil (photoinitiator no. 1).
Reaction SMILES: [CH3:1][C:2]12[C:8]([CH3:10])([CH3:9])[C:5]([C:11]([O:13][CH2:14][C@H:15]3[C@@H:17]([CH2:18][O:19][CH3:20])[C@@:16]3([CH3:33])[C:21]3[CH:26]=[C:25]([CH:27]([CH3:29])[CH3:28])[CH:24]=[C:23]([CH:30]([CH3:32])[CH3:31])[CH:22]=3)=[O:12])([CH2:6][CH2:7]1)[O:4][C:3]2=[O:34].COCC1[C@H](CO)C1(C)C1C=C(C(C)C)C=C(C(C)C)C=1.CCOC(C)=O>CCCCCC>[CH3:1][C:2]12[C:8]([CH3:9])([CH3:10])[C:5]([C:11]([O:13][CH2:14][C@H:15]3[C@H:17]([CH2:18][O:19][CH3:20])[C@@:16]3([CH3:33])[C:21]3[CH:26]=[C:25]([CH:27]([CH3:28])[CH3:29])[CH:24]=[C:23]([CH:30]([CH3:32])[CH3:31])[CH:22]=3)=[O:12])([CH2:6][CH2:7]1)[O:4][C:3]2=[O:34].[CH3:1][C:2]12[C:8]([CH3:9])([CH3:10])[C:5]([C:11]([O:13][CH2:14][C@@H:15]3[C@@H:17]([CH2:18][O:19][CH3:20])[C@:16]3([CH3:33])[C:21]3[CH:26]=[C:25]([CH:27]([CH3:28])[CH3:29])[CH:24]=[C:23]([CH:30]([CH3:32])[CH3:31])[CH:22]=3)=[O:12])([CH2:6][CH2:7]1)[O:4][C:3]2=[O:34]
Reactant: COC[C@@H]1[C@H](COC(=O)C23CCC(C)(C(=O)O2)C3(C)C)[C@]1(C)c1cc(C(C)C)cc(C(C)C)c1
Agent: COCC1[C@H](CO)C1(C)c1cc(C(C)C)cc(C(C)C)c1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: COC[C@@H]1[C@@H](COC(=O)C23CCC(C)(C(=O)O2)C3(C)C)[C@@]1(C)c1cc(C(C)C)cc(C(C)C)c1
Product: COC[C@H]1[C@H](COC(=O)C23CCC(C)(C(=O)O2)C3(C)C)[C@]1(C)c1cc(C(C)C)cc(C(C)C)c1
Yield: 41 %
Yield: 45 %

Procedure:
Following a procedure similar to that for the preparation of Intermediates 41 and 42 but using Intermediate 40a as the starting material and using 10% EtOAc in hexane as normal phase HPLC eluent afforded Intermediate 43a (25 mg, 45% yield) and Intermediate 44a (23 mg, 41% yield) as colorless oils:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[CH:18]=[C:17]([CH2:19][N:20]3[CH2:25][CH2:24][C:23](=O)[CH2:22][CH2:21]3)[CH:16]=[CH:15][N:14]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].[CH2:27]([NH2:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>>[CH2:27]([NH:34][CH:23]1[CH2:24][CH2:25][N:20]([CH2:19][C:17]2[CH:16]=[CH:15][N:14]=[C:13]([C:5]3[CH:4]=[C:3]([O:2][CH3:1])[C:8]([O:9][CH3:10])=[C:7]([O:11][CH3:12])[CH:6]=3)[CH:18]=2)[CH2:21][CH2:22]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: NCc1ccccc1
Reactant: COc1cc(-c2cc(CN3CCC(=O)CC3)ccn2)cc(OC)c1OC
Product: COc1cc(-c2cc(CN3CCC(NCc4ccccc4)CC3)ccn2)cc(OC)c1OC

Procedure:
1-[[2-(3,4,5-Trimethoxyphenyl)pyridin-4-yl]methyl-4-piperidone (1.40 g) and benzylamine (0.51 g) was condensed in the same manner as described in Preparation Example 37 to give the title compound as yellow amorphous.