Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O.[OH-].[Li+].[C:4]([S:7][C:8]1[N:9]=[C:10]([CH3:20])[N:11](C(OC(C)(C)C)=O)[CH:12]=1)(=O)[CH3:5].BrCC1[C:33]2[CH2:32][CH2:31][N:30]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:29][CH2:28][C:27]=2[CH:26]=[CH:25][C:24]=1[Cl:41]>CO>[C:37]([O:36][C:34]([N:30]1[CH2:31][CH2:32][C:33]2[C:5]([CH2:4][S:7][C:8]3[NH:9][C:10]([CH3:20])=[N:11][CH:12]=3)=[C:24]([Cl:41])[CH:25]=[CH:26][C:27]=2[CH2:28][CH2:29]1)=[O:35])([CH3:40])([CH3:39])[CH3:38]
Reactant: CC(=O)Sc1cn(C(=O)OC(C)(C)C)c(C)n1
Reactant: CC(C)(C)OC(=O)N1CCc2ccc(Cl)c(CBr)c2CC1
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: Cc1ncc(SCc2c(Cl)ccc3c2CCN(C(=O)OC(C)(C)C)CC3)[nH]1
Reaction time: 0.5 h
Yield: 77.5 %

Procedure:
Add lithium hydroxide hydrate (42 mg, 1 mmol) to a stirred solution of 4-acetylsulfanyl-1-tert-butoxycarbonyl-2-methyl-imidazole (290 mg, 1.13 mmol) and 6-bromomethyl-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (368 mg, 0.98 mmol) in methanol (12 mL) and stir the resulting mixture for 30 min. Partition the mixture between EtOAc and water and extract the aqueous phase three times with EtOAc. Dry the combined organic extracts over MgSO4, filter, and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel (40 g) eluting with hexane/EtOAc [100:0 (5 min), 19:1 (5 min), 85:15 (5 min), 4:1; flow rate: 50 mL/min] to give 3-tert-butoxycarbonyl-7-chloro-6-(2-methyl-3H-imidazol-4-ylthiomethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (310 mg, 54%). MS (ES+) m/z: 508 (M+H)+.
Reaction SMILES: C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.[F:19][C:20]1[CH:21]=[C:22]([CH2:27][C:28]([OH:30])=[O:29])[CH:23]=[C:24]([CH3:26])[CH:25]=1.[Br:31]N1C(=O)CCC1=O.O>C(Cl)Cl>[Br:31][CH2:26][C:24]1[CH:23]=[C:22]([CH2:27][C:28]([OH:30])=[O:29])[CH:21]=[C:20]([F:19])[CH:25]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1cc(F)cc(CC(=O)O)c1
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClCCl
Solvent: O
Product: O=C(O)Cc1cc(F)cc(CBr)c1

Procedure:
Benzoyl peroxide (0.05 g) was added to a mixture of 2-(3-fluoro-5-methylphenyl)acetic acid (0.518 g) and N-bromosuccinimide (0.6 g) in DCM (10 mL). The reaction was heated at reflux for 1 h. DCM (10 mL) and water (20 mL) were added and the organic phase separated. The organic layer was washed with brine (20 mL), dried over sodium sulphate, filtered and evaporated in vacuo. The residue was triturated with toluene and the resulting white solid removed by filtration. The mother liquors were evaporated in vacuo to give the subtitled compound as a white solid which was used in the next step without further purification. Yield 0.38 g.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCN(CC)CC.[Br:27][C:28]1[CH:61]=[CH:60][C:31]([C:32]([NH:34][NH:35][C:36](=[O:59])[C@H:37]([NH:48][C:49]2[CH:54]=[CH:53][C:52]([C:55]#[N:56])=[C:51]([Cl:57])[C:50]=2[CH3:58])[C@@H:38]([O:40][Si:41]([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42])[CH3:39])=O)=[CH:30][CH:29]=1>C(Cl)Cl>[Br:27][C:28]1[CH:29]=[CH:30][C:31]([C:32]2[O:59][C:36]([C@H:37]([NH:48][C:49]3[CH:54]=[CH:53][C:52]([C:55]#[N:56])=[C:51]([Cl:57])[C:50]=3[CH3:58])[C@@H:38]([O:40][Si:41]([C:44]([CH3:46])([CH3:47])[CH3:45])([CH3:42])[CH3:43])[CH3:39])=[N:35][N:34]=2)=[CH:60][CH:61]=1
Reactant: Cc1c(N[C@@H](C(=O)NNC(=O)c2ccc(Br)cc2)[C@H](C)O[Si](C)(C)C(C)(C)C)ccc(C#N)c1Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1c(N[C@@H](c2nnc(-c3ccc(Br)cc3)o2)[C@H](C)O[Si](C)(C)C(C)(C)C)ccc(C#N)c1Cl
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 88.5 %

Procedure:
To a solution of triphenylphosphine (4.23 g, 16.1 mmol) in DCM (200 mL) was added 12 (4.1 g, 16.2 mmol) at 0° C. After 12 was dissolved completely, Et3N (4.5 mL, 32.3 mmol) was added, followed by a solution of 4-bromo-N′-((2R,3S)-3-(tert-butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)butanoyl)-benzohydrazide (4.68 g, 8.1 mmol) in DCM (100 mL). The reaction mixture was allowed to warm to room temperature and stirred for additional 15 min. The reaction was quenched with saturated sodium thiosulfate (50 mL) and diluted with DCM (400 mL). The organic layer was separated and washed with water, brine, dried over Na2SO4, filtered and concentrated. The resulting residue was purified by flash chromatography to provide the title compound (4.03 g, 89%), which was used directly in the next step
Reaction SMILES: [CH3:1][C:2]1[C:3]([O:20][CH2:21][C:22]([F:25])([F:24])[F:23])=[CH:4][CH:5]=[N:6][C:7]=1[CH2:8][S+:9]([O-:19])[C:10]1[NH:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=2[N:18]=1.[CH:26]([NH2:29])([CH3:28])[CH3:27]>CC(OC)(C)C>[CH3:1][C:2]1[C:3]([O:20][CH2:21][C:22]([F:25])([F:23])[F:24])=[CH:4][CH:5]=[N:6][C:7]=1[CH2:8][S+:9]([O-:19])[C:10]1[NH:18][C:17]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[N:11]=1.[CH:26]([NH3+:29])([CH3:28])[CH3:27]
Reactant: CC(C)N
Agent: Cc1c(OCC(F)(F)F)ccnc1C[S+]([O-])c1nc2ccccc2[nH]1
Solvent: COC(C)(C)C
Product: CC(C)[NH3+]
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Dexlansoprazole (2 g) in amorphous form was dissolved in MTBE (50 mL) followed by the addition of isopropyl amine (3 mL). After stirring at room temperature for 30 minutes, the resulting suspension was filtered, washed with MTBE (10 mL) and dried in vacuo at 20-25° C. to provide dexlansoprazole isopropylammonium salt (2.1 g). Molar ratio of dexlansoprazole to isopropyl amine is 1:1 by 1H NMR.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH:11]([C:25]2[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=2[F:32])[C:12]2[C:17]([F:18])=[CH:16][N:15]=[C:14]([CH2:19][CH2:20][C:21]([O:23]C)=[O:22])[CH:13]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[OH-].[Na+].Cl>CO.O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH:11]([C:25]2[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=2[F:32])[C:12]2[C:17]([F:18])=[CH:16][N:15]=[C:14]([CH2:19][CH2:20][C:21]([OH:23])=[O:22])[CH:13]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: COC(=O)CCc1cc(C(c2cc(F)ccc2F)S(=O)(=O)c2ccc(Cl)cc2)c(F)cn1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)CCc1cc(C(c2cc(F)ccc2F)S(=O)(=O)c2ccc(Cl)cc2)c(F)cn1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 100 %

Procedure:
To a solution of methyl 3-[4-[(4-chlorophenylsulfonyl)(2,5-difluorophenyl)methyl]-5-fluoropyridin-2-yl]propionate (150 mg, 0.310 mmol) in a mixture of methanol (2 ml) and tetrahydrofuran (2 ml) was added a 1N aqueous sodium hydroxide solution. The resulting mixture was stirred at room temperature for 10 minutes. The reaction mixture was made weakly acidic by the addition of 1N hydrochloric acid, followed by extraction with dichloromethane. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure to give the title compound (145 mg, 0.310 mmol, quant.) as a white powder.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)(=O)[CH3:2].[C:10]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])#[N:11].C([O-])(=O)C.[NH4+]>C(OCC)(=O)C.C(O)(=O)C.C1C=CC=CC=1>[CH2:16]([O:15][C:13](=[O:14])[C:12]([C:10]#[N:11])=[C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:2])[CH3:17]
Reactant: CCOC(=O)CC#N
Reactant: CC(=O)c1ccccc1
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Solvent: c1ccccc1
Product: CCOC(=O)C(C#N)=C(C)c1ccccc1
Temperature: 25 °C
Reaction time: 10 h

Procedure:
A mixture of acetophenone (50 mmole), ethyl cyanoacetate (50 mmole), acetic acid (1.14 mL), ammonium acetate (400 mg), and benzene (50 mL) was heated to reflux in a Dean-Stark apparatus. After approximately 10 hours, additional ethyl cyanoacetate (50 mmole), acetic acid (1.14 mL), and ammonium acetate (400 mg) are added. After an additional 10 hours, the reaction was cooled to room temperature, diluted with ethyl acetate (30 mL), washed with water (240 mL), brine (40 mL), and dried (Na2SO4). After filtering, the extract was concentrated in vacuo and the desired product, as a mixture of E- and Z-isomers, was isolated by column chromatography on silica gel, eluting with 5% ethyl acetate/petroleum ether, affording an oil that solidified on standing at room temperature.
Reaction SMILES: [CH:1]1[CH2:8][CH2:7][CH:6]=[CH:5][CH2:4][CH2:3][CH:2]=1.C(O)C>[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Rh].[Rh].[Rh].[Rh].CC(C)=O>[CH:1]1[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.[CH2:1]1[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: C1=CCCC=CCC1
Agent: [Rh]
Agent: [C-]#[O+]
Solvent: CCO
Solvent: CC(C)=O
Product: C1=CCCCCCC1
Product: C1CCCCCCC1
Reaction time: 0.17 h

Procedure:
0.3 ml of 1,5-cyclooctadiene, 32 ml of ethanol, 8 ml of acetone and 3 mg of tetrarhodiumdodecacarbonyl [Rh4 (CO)12 ] were fed into the same quartz cell as that used in the Example 1. Nitrogen gas was bubbled through the contents under stirring for 10 minutes and thereafter, the irradiation of the cell with light was started. The stirring was conducted with a magnetic stirrer. The reaction cell was put in a quartz-window thermostatic chamber to keep the reaction temperature at 20° C. In the irradiation, the rays which were emitted from a 500-W high-pressure mercury lamp set on an irradiation apparatus as an outer light source and passed through a filter UV-25, mfd. by Toshiba Corporation, were used. After the irradiation had been conducted for 5 hours in such a manner, the reaction solution was analyzed by gas chromatography. Cyclooctene was obtained in a yield of 88% with the formation of cyclooctane in a yield of 12%. No 1,5-cyclooctadiene was detected by the gas chromatography.
Reaction SMILES: [CH3:1][NH2:2].[CH3:3][O:4][C:5]1[CH:21]=[CH:20][C:8]([CH2:9][O:10][C:11]2[CH:18]=[CH:17][C:14]([CH:15]=O)=[CH:13][C:12]=2[Br:19])=[CH:7][CH:6]=1.[BH4-].[Na+]>CO>[CH3:3][O:4][C:5]1[CH:21]=[CH:20][C:8]([CH2:9][O:10][C:11]2[CH:18]=[CH:17][C:14]([CH2:15][NH:2][CH3:1])=[CH:13][C:12]=2[Br:19])=[CH:7][CH:6]=1
Reactant: COc1ccc(COc2ccc(C=O)cc2Br)cc1
Reactant: CN
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CNCc1ccc(OCc2ccc(OC)cc2)c(Br)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 88 %

Procedure:
To a solution of 2M methylamine in MeOH (30 mL) was added intermediate 32 (2.91 g, 9.1 mmol, 1 eq). After stirring this mixture at room temperature for 30 min, the solvent was removed and the residue was partitioned between saturated NaHCO3 and DCM (2×100 mL). The organic layer was dried (Na2SO4) and concentrated. The resultant residue was dissolved in MeOH (25 mL) and, after addition of sodium borohydride (1.0 g, 27.6 mmol, 3 eq), the mixture was stirred at room temperature for 1 h. Solvent was removed and the residue was partitioned between a Na2CO3 solution and CHCl3. The resultant organic layer was dried (Na2SO4) and concentrated in vacuo to give 2.7 g, (88%) of (4-(4-methoxybenzyloxy)-3-bromophenyl)-N-methylmethanamine (33).
Reaction SMILES: [Br:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:22]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([S:16][C:17]([F:20])([F:19])[F:18])=[C:12]([F:21])[CH:11]=1)=[O:8].[NH:24]1[CH2:28][CH2:27][C@@H:26]([OH:29])[CH2:25]1>>[Br:1][C:2]1[C:3]([N:24]2[CH2:28][CH2:27][C@@H:26]([OH:29])[CH2:25]2)=[N:4][CH:5]=[C:6]([CH:22]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([S:16][C:17]([F:20])([F:19])[F:18])=[C:12]([F:21])[CH:11]=1)=[O:8]
Reactant: O[C@@H]1CCNC1
Reactant: O=C(Nc1ccc(SC(F)(F)F)c(F)c1)c1cnc(Cl)c(Br)c1
Product: O=C(Nc1ccc(SC(F)(F)F)c(F)c1)c1cnc(N2CC[C@@H](O)C2)c(Br)c1

Procedure:
The title compound was prepared in an analogous fashion to that described in Stage 33.1 using 5-bromo-6-chloro-N-(3-fluoro-4-((trifluoromethyl)thio)phenyl)nicotinamide (Stage 205.2) and (R)-pyrrolidin-3-ol to afford an off-white crystalline solid. HPLC (Condition 4) tR=6.11 min, UPLC-MS (Condition 3) tR=1.23 min, m/z=480.1 [M+H]+.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]1[C:11](Cl)=[O:12].[CH3:14][O:15][C:16]1[CH:22]=[C:21]([B:23]2[O:27][C:26]([CH3:29])([CH3:28])[C:25]([CH3:31])([CH3:30])[O:24]2)[CH:20]=[CH:19][C:17]=1[NH2:18].C(N(C(C)C)C(C)C)C>ClCCl>[CH3:14][O:15][C:16]1[CH:22]=[C:21]([B:23]2[O:24][C:25]([CH3:30])([CH3:31])[C:26]([CH3:29])([CH3:28])[O:27]2)[CH:20]=[CH:19][C:17]=1[NH:18][C:11]([C:3]1[N:2]([CH3:1])[C:10]2[C:5]([CH:4]=1)=[CH:6][CH:7]=[CH:8][CH:9]=2)=[O:12]
Reactant: Cn1c(C(=O)Cl)cc2ccccc21
Reactant: COc1cc(B2OC(C)(C)C(C)(C)O2)ccc1N
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc(B2OC(C)(C)C(C)(C)O2)ccc1NC(=O)c1cc2ccccc2n1C
Temperature: 25 °C
Reaction time: 18 h
Yield: 70.1 %

Procedure:
To a solution containing 1-methyl-1H-2-indolecarbonyl chloride (5.44 g, 0.0281 mol) and 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (7.00 g, 0.0281 mol) in anhydrous dichloromethane (150 mL), N-ethyl-N,N-diisopropylamine (4.9 mL, 0.0309 mol) was added dropwise at 0° C. and the resulting solution was stirred at ambient temperature under an atmosphere of nitrogen for 18 hours. The reaction mixture was concentrated under reduced pressure and the residue was partitioned between water (150 mL) and ethyl acetate (150 mL), The organic phase was washed with brine, dried with magnesium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography on silica using ethyl acetate/n-heptane (1:6)) as mobile phase to yield N2-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-methyl-1H-2-indolecarboxamide (8.0 g, 0.0197 mol) as a white solid.
Reaction SMILES: [H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[C:14]([O:18][C:19]([NH:21][C@@H:22]([C@@H:47]([O:58][Si:59]([C:62]([CH3:65])([CH3:64])[CH3:63])([CH3:61])[CH3:60])[C:48]1[CH:53]=[CH:52][C:51]([C:54]([F:57])([F:56])[F:55])=[CH:50][CH:49]=1)[CH2:23][N:24]([C:32]1[S:33][C:34]([C:37]2[CH:42]=[CH:41][C:40]([N+:43]([O-:45])=[O:44])=[C:39](F)[CH:38]=2)=[N:35][N:36]=1)[C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:20])([CH3:17])([CH3:16])[CH3:15]>O1CCOCC1>[C:27]([O:26][C:25]([N:24]([CH2:23][C@@H:22]([NH:21][C:19]([O:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:20])[C@@H:47]([O:58][Si:59]([C:62]([CH3:63])([CH3:64])[CH3:65])([CH3:61])[CH3:60])[C:48]1[CH:53]=[CH:52][C:51]([C:54]([F:57])([F:56])[F:55])=[CH:50][CH:49]=1)[C:32]1[S:33][C:34]([C:37]2[CH:42]=[CH:41][C:40]([N+:43]([O-:45])=[O:44])=[C:39]([CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:3]([O:11][CH2:12][CH3:13])=[O:10])[CH:38]=2)=[N:35][N:36]=1)=[O:31])([CH3:28])([CH3:29])[CH3:30]
Reactant: CCOC(=O)CC(=O)OCC
Reactant: CC(C)(C)OC(=O)N[C@H](CN(C(=O)OC(C)(C)C)c1nnc(-c2ccc([N+](=O)[O-])c(F)c2)s1)[C@@H](O[Si](C)(C)C(C)(C)C)c1ccc(C(F)(F)F)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1COCCO1
Product: CCOC(=O)C(C(=O)OCC)c1cc(-c2nnc(N(C[C@@H](NC(=O)OC(C)(C)C)[C@@H](O[Si](C)(C)C(C)(C)C)c3ccc(C(F)(F)F)cc3)C(=O)OC(C)(C)C)s2)ccc1[N+](=O)[O-]
Reaction time: 0.25 h
Yield: 99.4 %

Procedure:
To a solution of sodium hydride (60% dispersion in mineral oil, 0.15 g, 3.74 mmol) in dioxane (2 mL) was added a solution of diethyl malonate (0.57 mL, 3.74 mmol) in dioxane (3 mL). The mixture was stirred for 15 minutes and then a solution of tert-butyl ((2R,3S)-2-((tert-butoxycarbonyl)amino)-3-((tert-butyl(dimethyl)silyl)oxy)-3-(4-(trifluoromethyl)phenyl)propyl)(5-(3-fluoro-4-nitrophenyl)-1,3,4-thiadiazol-2-yl)carbamate (0.58 g, 0.75 mmol) in dioxane (3 mL) was added. The reaction mixture was stirred 16 hours, concentrated in vacuo, and the reaction was quenched with saturated NH4Cl. The mixture was extracted with EtOAc three times. The organic phase was dried over Na2SO4, concentrated in vacuo and purified by chromatography on silica gel (0-15% EtOAc-hexane) to provide the product as a yellow solid (0.68 g, 99%). LCMS (API-ES) m/z: 856 (M+H+-56).
Reaction SMILES: [CH2:1]([N:8]([C:13]1[CH:18]=[N:17][N:16]([CH3:19])[C:15](=[O:20])[C:14]=1[Cl:21])[CH2:9][CH2:10][CH2:11]O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:22]CCl.S(Cl)(Cl)=O>CN(C1C=CN=CC=1)C>[CH2:1]([N:8]([C:13]1[CH:18]=[N:17][N:16]([CH3:19])[C:15](=[O:20])[C:14]=1[Cl:21])[CH2:9][CH2:10][CH2:11][Cl:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: ClCCl
Reactant: Cn1ncc(N(CCCO)Cc2ccccc2)c(Cl)c1=O
Agent: CN(C)c1ccncc1
Solvent: O=S(Cl)Cl
Product: Cn1ncc(N(CCCCl)Cc2ccccc2)c(Cl)c1=O
Reaction time: 14 h
Yield: 91 %

Procedure:
To a solution of 10.00 g (32 mmol) of 5-[N-benzyl-N-(3-hydroxypropyl)amino]-4-chloro-2-methyl-3(2H)-pyridazinone in 100 ml of dichloromethane 3.5 ml (5.5 g, 46 mmol) of thionyl chloride are added dropwise while stirring. If necessary, a catalytic amount of 4-(N,N-dimethyl amino)pyridine is added to the solution. The reaction mixture is boiled for 14 hours, then cooled and evaporated. The evaporation residue is triturated with diethyl ether. The crystals are filtered off and washed with diethyl ether. In this way 9.50 g (95%) of the title compound are obtained with a melting point of 92-93° C.
Reaction SMILES: [NH2:1][C:2]1[N+:7]([O-:8])=[C:6]([NH2:9])[CH:5]=[C:4]([N:10]2[CH2:15][CH:14]=[CH:13][CH2:12][CH2:11]2)[N:3]=1.C(Cl)Cl.[CH2:19]([O:23][C:24](Cl)=[O:25])[CH:20]([CH3:22])[CH3:21]>C(N(CC)CC)C>[N:10]1([C:4]2[N:3]=[C:2]([NH:1][C:24]([O:23][CH2:19][CH:20]([CH3:22])[CH3:21])=[O:25])[N+:7]([O-:8])=[C:6]([NH:9][C:24]([O:23][CH2:19][CH:20]([CH3:22])[CH3:21])=[O:25])[CH:5]=2)[CH2:11][CH:12]=[CH:13][CH2:14][CH2:15]1
Reactant: CC(C)COC(=O)Cl
Reactant: Nc1cc(N2CC=CCC2)nc(N)[n+]1[O-]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)COC(=O)Nc1cc(N2CC=CCC2)nc(NC(=O)OCC(C)C)[n+]1[O-]
Reaction time: 2 h

Procedure:
20.7 G. of 2,4-diamino-6-[3,6-dihydro-1(2H)-pyridyl]pyrimidine-3-oxide are mixed with 250 ml. of methylene chloride and 35 ml. of triethylamine and cooled to 5° C. 40 Ml. of chloroformic acid isobutyl ester are added dropwise while stirring. After completion of the addition, the mixture is stirred at 5° C. for 15 minutes and then at room temperature for 2 hours. The solution is treated with 200 ml. of water and extracted with methylene chloride. The organic phase is evaporated and the residue is crystallized from ethanol. There is obtained diisobutyl 6-[3,6-dihydro-1(2H)-pyridyl]-2,4-pyrimidine-dicarbamate-3-oxide, having a melting point of 137°-139° C. (decomposition).
Reaction SMILES: C(O)C.[OH-].[Na+].[F:6][C:7]1[CH:12]=[CH:11][C:10]([C@@H:13]([NH:15][C:16]2[N:21]=[C:20]([N:22]3[CH:26]=[C:25]([C:27]([O:29]CC)=[O:28])[CH:24]=[N:23]3)[CH:19]=[C:18]([NH:32][C:33]3[CH:38]=[N:37][CH:36]=[CH:35][N:34]=3)[N:17]=2)[CH3:14])=[CH:9][CH:8]=1>O1CCCC1>[F:6][C:7]1[CH:12]=[CH:11][C:10]([C@@H:13]([NH:15][C:16]2[N:21]=[C:20]([N:22]3[CH:26]=[C:25]([C:27]([OH:29])=[O:28])[CH:24]=[N:23]3)[CH:19]=[C:18]([NH:32][C:33]3[CH:38]=[N:37][CH:36]=[CH:35][N:34]=3)[N:17]=2)[CH3:14])=[CH:9][CH:8]=1
Reactant: CCOC(=O)c1cnn(-c2cc(Nc3cnccn3)nc(N[C@@H](C)c3ccc(F)cc3)n2)c1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: C[C@H](Nc1nc(Nc2cnccn2)cc(-n2cc(C(=O)O)cn2)n1)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 42.7 %

Procedure:
2 ml of ethanol, 1 ml of tetrahydrofuran and 80 μl of 12% sodium hydroxide aqueous solution were added to 35 mg of ethyl (S)-1-{2-[1-(4-fluorophenyl)ethylamino]-6-(pyrazin-2-ylamino)pyrimidin-4-yl}-1H-pyrazole-4-carboxylate, and the mixture was stirred at room temperature for 18 hours. 160 μl of 12% sodium hydroxide aqueous solution was added thereto, and the mixture was further stirred for 3 hours. Ethanol was distilled off. The obtained residue was diluted with ethanol, and diluted with water, and the ply of the mixture was adjusted to 7 by using 10% hydrochloric acid, the mixture was subjected to extraction with ethyl acetate, and the organic layer was washed with brine, and then dried over magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 14 mg of the objective compound as white powder.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:18][CH2:17][C:16]2[C:11](=[CH:12][C:13]([O:19][CH2:20][C:21]([OH:23])=O)=[CH:14][CH:15]=2)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O[N:25]1[C:29](=O)[CH2:28][CH2:27][C:26]1=O.C1(N=C=NC2CCCCC2)CCCCC1.C(N)CCC>C(#N)C.C(OCC)C>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:18][CH2:17][C:16]2[C:11](=[CH:12][C:13]([O:19][CH2:20][C:21]([NH:25][CH2:26][CH2:27][CH2:28][CH3:29])=[O:23])=[CH:14][CH:15]=2)[CH2:10]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]
Reactant: CC(C)(C)OC(=O)N[C@H]1CCc2ccc(OCC(=O)O)cc2C1
Reactant: O=C1CCC(=O)N1O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CCOCC
Solvent: CCCCN
Solvent: CC#N
Product: CCCCNC(=O)COc1ccc2c(c1)C[C@@H](NC(=O)OC(C)(C)C)CC2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
4 g (0.0013 mole) of (2S)-2-tert-butoxycarbonylamino-7-hydroxycarbonylmethoxy-tetralin and 1.66 g (0.0143 mole) of N-hydroxysuccinimide in 40 ml of acetonitrile were stirred at ambient temperature for 3 hours and 2.95 g (0.0143 mole) of DCC (dicyclohexylcarbodiimide) in 15 ml of ethyl ether were added. 1.3 ml (0.0195 mole) of n-butylamine were then added and it was stirred at ambient temperature overnight. The solvent was evaporated off, the residue was taken up in water; it was extracted with ethyl acetate. The organic phase was washed with an aqueous sodium bicarbonate solution, dried and the solvent was evaporated off under reduced pressure. The residue was taken up in a 1:1 ethyl acetate/hexane mixture; the precipitate formed was filtered off and oven dried. The product of the heading was obtained as a white solid.
Reaction SMILES: [CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:9]([O:11][SiH:12]([O:16][CH2:17][CH3:18])[O:13][CH2:14][CH3:15])[CH3:10].P(OCC(CC)CCCC)(OCC(CC)CCCC)(O)=O>[Pt].C1(C)C=CC=CC=1>[CH2:1]([Si:12]([O:16][CH2:17][CH3:18])([O:13][CH2:14][CH3:15])[O:11][CH2:9][CH3:10])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: C=Cc1ccccc1
Reactant: CCO[SiH](OCC)OCC
Agent: [Pt]
Agent: CCCCC(CC)COP(=O)(O)OCC(CC)CCCC
Solvent: Cc1ccccc1
Product: CCO[Si](CCc1ccccc1)(OCC)OCC
Yield: 16 %

Procedure:
Reaction between styrene and triethoxysilane with platinum catalyst in the presence of bis(2-ethylhexyl) hydrogenphosphate (C4H9CH(C2H5)CH2O)2P(═O)OH). 0.334 g Styrene and 0.540 g triethoxysilane were introduced into a glass tube, and 3 mg of bis(2-ethylhexyl) hydrogenphosphate were added using a microsyringe. 0.8 mg Of a toluene solution of a 0-valent platinum complex of divinylsiloxane (0.4 wt % platinum content) was added. The tube was sealed with Teflon tape and a septum and placed in a 100° C. oil bath where it was heated for 1 hour. After cooling, the tube contents were analyzed by gas chromatography revealing a styrene conversion of about 29% and a phenethyl triethoxysilane yield of 16%. The ratio between the phenethyl triethoxysilane and the (α-methylbenzyl)triethoxysilane was 5.8:1.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:45])[NH:4][CH:5]([C:19](=[O:44])[NH:20][CH2:21][CH2:22][CH2:23][CH2:24][CH:25]([N:28]([S:33]([C:36]1[CH:41]=[CH:40][C:39]([NH2:42])=[C:38]([F:43])[CH:37]=1)(=[O:35])=[O:34])[CH2:29][CH:30]([CH3:32])[CH3:31])[CH2:26][OH:27])[CH:6]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.COC(=O)N[C@H](C(=O)NCCCC[C@H:70](N(S(C1C=CC(N)=CC=1)(=O)=O)CC(C)C)[CH2:71][O:72][P:73]([OH:76])([OH:75])=O)C(C1C=CC=CC=1)C1C=CC=CC=1.[B-](F)(F)(F)F.[B-](F)(F)(F)F.[CH2:104]1[N+]2(CCl)CC[N+](F)(CC2)[CH2:105]1>CC#N>[CH3:1][O:2][C:3](=[O:45])[NH:4][C@H:5]([C:19](=[O:44])[NH:20][CH2:21][CH2:22][CH2:23][CH2:24][C@H:25]([N:28]([S:33]([C:36]1[CH:41]=[CH:40][C:39]([NH2:42])=[C:38]([F:43])[CH:37]=1)(=[O:34])=[O:35])[CH2:29][CH:30]([CH3:32])[CH3:31])[CH2:26][O:27][P:73]([O:72][CH2:71][CH3:70])([O:75][CH2:104][CH3:105])=[O:76])[CH:6]([C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: F[N+]12CC[N+](CCl)(CC1)CC2
Reactant: COC(=O)NC(C(=O)NCCCCC(CO)N(CC(C)C)S(=O)(=O)c1ccc(N)c(F)c1)C(c1ccccc1)c1ccccc1
Reactant: COC(=O)N[C@H](C(=O)NCCCC[C@@H](COP(=O)(O)O)N(CC(C)C)S(=O)(=O)c1ccc(N)cc1)C(c1ccccc1)c1ccccc1
Agent: F[B-](F)(F)F
Solvent: CC#N
Product: CCOP(=O)(OCC)OC[C@H](CCCCNC(=O)[C@@H](NC(=O)OC)C(c1ccccc1)c1ccccc1)N(CC(C)C)S(=O)(=O)c1ccc(N)c(F)c1
Reaction time: 0.5 h
Yield: 48 %

Procedure:
The product of step A above, (1S,5S)-(1-{5-[(4-amino-benzenesulfonyl)-isobutyl-amino]-6-phosphonooxy hexylcarbamoyl}-2,2-diphenyl-ethyl)-carbamic acid methyl ester (0.555 g, 0.73 mmol) was dissolved in 5 mL MeCN. Selectfluor (0.26 g, 0.7 mmol) was added and the mixture stirred for 30 min. The mixture was purified by reverse phase preparative HPLC and lyophilized to yield 278 mg (48% yield) white solid.