Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3]([C@@H:5]([C@@H:7]([C@H:9]([C@@H:11]([CH2:13][OH:14])[OH:12])O)[OH:8])[OH:6])=[O:4].C(N(CCCCCC)CCCCCC)CCCCC>C(#N)C>[O:4]=[C:3]1[O:2][C@H:9]([C@H:11]([CH2:13][OH:14])[OH:12])[C:7]([OH:8])=[C:5]1[OH:6]
Reactant: COC(=O)[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO
Agent: CCCCCCN(CCCCCC)CCCCCC
Solvent: CC#N
Product: O=C1O[C@H]([C@@H](O)CO)C(O)=C1O
Temperature: 78 °C
Yield: 90.9 %

Procedure:
26.8 g (128.7 mmol) of ketogulonic acid methyl ester and 125 ml of acetonitrile were added under argon to a 500 ml sulphonation flask provided with a stirrer, thermometer, reflux condenser and 50 ml dropping funnel. Thereupon, the mixture was heated to 78° C. (reflux) while stirring. 34.7 g (100 mol %) of trihexylamine (99.4%) were then added dropwise within 15 minutes from the dropping funnel. The ester passed into solution completely after a reaction period of about 1 hour. After stirring for a total of 21/2 hours at reflux temperature, the orange-brown mixture was added to a rotary perforator gassed with nitrogen. Thereupon, the mixture was extracted continuously with about 500 ml of n-hexane for 20 hours. 1 hour after the beginning of the extraction, ascorbic acid crystallizes out slowly from the acetonitrile phase. After completion of the extraction, the content of the extractor was suction filtered. The yellowish crystals were washed with hexane and acetonitrile and dried overnight in a desiccator. There were obtained 20.6 g of ascorbic acid with a content of 99.5%, corresponding to a yield of 90.4%.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([C:12]2[CH2:21][CH2:20][C:19]3[C:14](=[CH:15][C:16]([C:22]4[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=4)=[CH:17][CH:18]=3)[CH:13]=2)=[O:11])=[CH:5][CH:4]=1.[OH:29][CH2:30][CH2:31][N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.C(=O)([O-])O.[Na+]>C1COCC1>[OH:29][CH2:30][CH2:31][N:32]1[CH2:37][CH2:36][N:35]([CH2:2][C:3]2[CH:8]=[CH:7][C:6]([NH:9][C:10]([C:12]3[CH2:21][CH2:20][C:19]4[C:14](=[CH:15][C:16]([C:22]5[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=5)=[CH:17][CH:18]=4)[CH:13]=3)=[O:11])=[CH:5][CH:4]=2)[CH2:34][CH2:33]1
Reactant: OCCN1CCNCC1
Reactant: Cc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(CCl)cc2)CC3)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(CN4CCN(CCO)CC4)cc2)CC3)cc1
Temperature: 25 °C

Procedure:
In THF (7 ml) was dissolved N-[4—(chloromethyl)-phenyl]-7—(4-methylphenyl)-3,4-dihydronaphthalene-2-carboxamide (150 mg), and to the mixture was added 1—(2-hydroxyethyl)piperazine (14 μl). The mixture was refluxed for 22 hours. The reaction mixture was cooled to room temperature, and to the mixture was added 5% sodium hydrogen carbonate solution (50 ml). The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate-hexane to give N-[4-[1—(2-hydroxyethyl)-4-piperazinylmethyl]phenyl]-7—(4-methylphenyl)-3,4-dihydronaphthalene-2-carboxamide (Compound 46) (158 mg) as colorless crystals.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([CH:8]([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[N:11]([CH2:21][CH3:22])[C:12]1[N:17]=[C:16]([CH2:18][OH:19])[CH:15]=[C:14]([CH3:20])[N:13]=1.C(N(CC)CC)C.[CH3:30][S:31](Cl)(=[O:33])=[O:32]>ClCCl>[Br:1][C:2]1[CH:7]=[C:6]([CH:8]([CH3:9])[CH3:10])[CH:5]=[CH:4][C:3]=1[N:11]([CH2:21][CH3:22])[C:12]1[N:17]=[C:16]([CH2:18][O:19][S:31]([CH3:30])(=[O:33])=[O:32])[CH:15]=[C:14]([CH3:20])[N:13]=1
Reactant: CS(=O)(=O)Cl
Reactant: CCN(c1nc(C)cc(CO)n1)c1ccc(C(C)C)cc1Br
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCN(c1nc(C)cc(COS(C)(=O)=O)n1)c1ccc(C(C)C)cc1Br
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 84.1 %

Procedure:
To a mixture of N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-hydroxymethyl-6-methylpyrimidinamine (1.57 g, 4.3 mmol), triethylamine(2.5 mL, 17 mmol) and dichloromethane (15 mL) at 0° C. under a nitrogen atmosphere was added methanesulfonyl chloride (0.54 g, 4.7 mmol) dropwise and the reaction mixture was stirred at 0° C. for 1.5 h. It was then washed successively with an ice-cold 1N HCl solution, a saturated NaHCO3 solution and a saturated NaCl solution. Drying the methylene chloride solution over MgSO4, filtration and removal of solvent in vacuo gave N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-methanesulfonyloxymethyl-6-methylpyrimidinamine as a clear colorless oil (1.6 g): NMR (CDCl3, 300 MHz): 7.5 (d, 1H, J=1), 7.25-7.1 (m, 2H), 6.5 (s, 1H), 5.05-4.9 (br s, 2H), 4.3-4.1 (m, 1H), 3.8-3.6 (m, 1H), 3.0-2.85 (m, 1H), 2.8-2.6 (br s, 3H), 2.5-2.25 (br m, 3H), 1.3 (d, 6H, J=8), 1.2 (t, 3H, J=8); CI-MS, 442, 444 (M+H).
Reaction SMILES: [NH:1]1[CH2:11][CH2:10][CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.Br[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[N:30]=[N:31][N:32]([CH2:34][CH3:35])[N:33]=2)=[CH:25][CH:24]=1>CS(C)=O.CO.C(OCC)(=O)C>[CH2:34]([N:32]1[N:31]=[N:30][C:29]([C:26]2[CH:27]=[CH:28][C:23]([CH2:22][N:1]3[CH2:2][CH2:3][CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:10][CH2:11]3)=[CH:24][CH:25]=2)=[N:33]1)[CH3:35]
Reactant: CCOC(=O)C1CCNCC1
Reactant: CCn1nnc(-c2ccc(CBr)cc2)n1
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Solvent: CO
Product: CCOC(=O)C1CCN(Cc2ccc(-c3nnn(CC)n3)cc2)CC1
Temperature: 25 °C
Reaction time: 72 h
Yield: 71.6 %

Procedure:
A solution of 16.0 grams (0.102 mole) of ethyl isonipecotate in 50 mL of DMSO and 66 mL of methanol was stirred, and 44 mL (0.256 mole) of N,N-diisopropylethylamine, followed by 22.8 grams (0.085 mole) of 5-[4-(bromomethyl)phenyl]-2-ethyl-1,2,3,4-tetraazole were added. Upon completion of addition, the reaction mixture was stirred at ambient temperature for about 72 hours. After this time, the reaction mixture was diluted with 130 mL of ethyl acetate, and washed with a 1:1 solution of an aqueous solution saturated with sodium chloride and water. The organic layer was then washed with an aqueous solution saturated with sodium chloride and water, dried with sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel using mixtures of methylene chloride and acetone. The appropriate fractions were combined and concentrated under reduced pressure, yielding 20.9 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: [C:1]([C:5]1[N:10]=[CH:9][C:8]([C:11]2[N:12]([C:32]([N:34]3[CH2:39][CH2:38][N:37]([CH2:40][C:41]([OH:43])=O)[CH2:36][CH2:35]3)=[O:33])[C@@:13]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)([CH3:24])[C@@:14]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)([CH3:16])[N:15]=2)=[C:7]([O:44][CH2:45][CH3:46])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:47][CH2:48][C:49]1[CH:54]=[CH:53][N:52]=[CH:51][CH:50]=1>>[C:1]([C:5]1[N:10]=[CH:9][C:8]([C:11]2[N:12]([C:32]([N:34]3[CH2:39][CH2:38][N:37]([CH2:40][C:41]([NH:47][CH2:48][C:49]4[CH:54]=[CH:53][N:52]=[CH:51][CH:50]=4)=[O:43])[CH2:36][CH2:35]3)=[O:33])[C@@:13]([C:25]3[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=3)([CH3:24])[C@@:14]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)([CH3:16])[N:15]=2)=[C:7]([O:44][CH2:45][CH3:46])[CH:6]=1)([CH3:2])([CH3:4])[CH3:3]
Reactant: NCc1ccncc1
Reactant: CCOc1cc(C(C)(C)C)ncc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@@](C)(c2ccc(Cl)cc2)N1C(=O)N1CCN(CC(=O)O)CC1
Product: CCOc1cc(C(C)(C)C)ncc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@@](C)(c2ccc(Cl)cc2)N1C(=O)N1CCN(CC(=O)NCc2ccncc2)CC1

Procedure:
In a manner analogous to the method described in example 99, {4-[(4S,5R)-2-(6-tert-Butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-acetic acid was coupled with 4-(Aminomethyl)pyridine (Aldrich) to give the title compound. HR-MS (ES, m/z) calculated for C41H48Cl2N7O3 [(M+H)+] 756.319, observed 756.3194.
Reaction SMILES: CC[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[C:11]([OH:15])(C)(C)C.[Se](=O)=O.C1(C(C)=C)C=CC=CC=1>C(Cl)Cl.C(O)(=O)C>[OH:15][CH2:11][C:9]([C:8]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[CH2:10]
Reactant: CC(C)(C)O
Reactant: CCCCCCCCCC
Agent: C=C(C)c1ccccc1
Agent: O=[Se]=O
Solvent: CC(=O)O
Solvent: ClCCl
Product: C=C(CO)c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 59 %

Procedure:
A 12.5 ml of decane solution of 5 to 6 mol/L of per-tert-butylalcohol is diluted with 50 ml of methylene chloride, then 111 mg of selenium dioxide and 90.1 mg of an acetic acid were added thereto to react while stirring at room temperature for 30 min. Then, 6.5 ml of 2-phenylpropene was added to the reaction solution to react while stirring for 72 hours, followed by condensation under reduced pressure, and purification by silica gel column chromatography to obtain 3.98 g of 3-hydroxy-2-phenylpropene (yield: 59%). Measurement results by 1H-NMR and 13C-NMR of 3-hydroxy-2-phenylpropene obtained are shown below.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]2[C:3]=1[CH2:4][CH2:5][C@@H:6]2[OH:12].N1C=CN=C1.[C:18]([Si:22]([CH3:25])([CH3:24])Cl)([CH3:21])([CH3:20])[CH3:19].O>CN(C)C=O>[Br:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]2[C:3]=1[CH2:4][CH2:5][C@@H:6]2[O:12][Si:22]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:25])[CH3:24]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: O[C@H]1CCc2c(Br)ccc(F)c21
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)[Si](C)(C)O[C@H]1CCc2c(Br)ccc(F)c21
Temperature: 25 °C
Reaction time: 2 h

Procedure:
(S)-4-bromo-7-fluoro-2,3-dihydro-1H-inden-1-ol (6.8 g) and imidazol (5 g) are dissolved at 0° C. in N,N-dimethylformamide (NMP, 25 mL), treated with tert.-butyldimethylchlorosilane (6.3 g) and stirred for 2 hours at room temperature. Water is added and the mixture is stirred for 10 minutes. Then the mixture is partitioned between 1 M hydrochloric acid and ethyl acetate. The organic phase is dried (MgSO4) and concentrated to give the title compound. Yield: 9.25 g.
Reaction SMILES: [C:1]([NH:20][CH2:21][C:22]1[O:23][CH2:24][CH2:25][CH2:26][CH:27]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-:28].[Na+].OO>O1CCCC1>[C:1]([NH:20][CH2:21][CH:22]1[CH:27]([OH:28])[CH2:26][CH2:25][CH2:24][O:23]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C1=C(CNC(c2ccccc2)(c2ccccc2)c2ccccc2)OCCC1
Reactant: [OH-]
Agent: OO
Agent: [Na+]
Solvent: C1CCOC1
Product: OC1CCCOC1CNC(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 79.6 %

Procedure:
A solution of a borane-tetrahydrofuran complex in tetrahydrofuran (1 M, 187 mL, 187 mmol) was added dropwise to a solution of 2-(tritylamino)methyl-5,6-dihydro-4H-pyran (22.2 g, 62.4 mmol) in tetrahydrofuran (180 mL) at room temperature over 20 minutes. After stirring at room temperature for 2.5 hours, the reaction solution was ice-cooled, and a 3N sodium hydroxide solution (208 mL, 624 mmol) was added dropwise over 10 minutes. Subsequently a 31% hydrogen peroxide solution (69 mL, 629 mmol) was added dropwise at the same temperature over 10 minutes, and then the mixture was stirred at room temperature for one hour. The reaction solution was extracted with diethyl ether (2×300 mL). The combined organic layers were washed with water (300 mL) and brine (300 mL), and then dried over anhydrous sodium sulfate and filtered. The solvent was evaporated under reduced pressure, and then the residue was suspended in a mixed solvent of dichloromethane/hexane (1:1, 80 mL). The insoluble material was removed by filtration, and then the filtrate was evaporated under reduced pressure to give 18.54 g (80%) of the title compound as a pale yellow gummy solid.
Reaction SMILES: [C:1]([NH:8][C@H:9]([C:17]([OH:19])=O)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[NH:20]1[CH2:25][CH2:24][NH:23][CH2:22][C:21]1=[O:26].[OH-].[Na+]>ClCCl.CN(C)C=O>[C:4]([O:3][C:1](=[O:2])[NH:8][C@@H:9]([CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:17](=[O:19])[N:23]1[CH2:24][CH2:25][NH:20][C:21](=[O:26])[CH2:22]1)([CH3:5])([CH3:6])[CH3:7]
Reactant: O=C1CNCCN1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)C(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)C(=O)N1CCNC(=O)C1

Procedure:
BOC-L-phenylalanine (530 mg, 2 mmol) and piperazin-2-one (J. Am. Chem. Soc. 62 1202 (1940), 200 mg, 2 mmol) were coupled according to procedure A (2:1 dichloromethane/dimethylformamide reaction solvent, washed with 1 N NaOH after acid washes) and the product used without further purification. Yield 404 mg, 58%.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]2[NH:12][C:13](=[O:15])[NH:14][C:7]=12.[F:19][C:20]([F:31])([F:30])[C:21]1[CH:22]=[C:23]([CH:27]=[CH:28][CH:29]=1)[C:24](Cl)=[O:25]>>[O:15]=[C:13]1[NH:12][C:8]2=[N:9][CH:10]=[CH:11][C:6]([O:5][C:4]3[CH:3]=[C:2]([NH:1][C:24](=[O:25])[C:23]4[CH:27]=[CH:28][CH:29]=[C:21]([C:20]([F:19])([F:30])[F:31])[CH:22]=4)[CH:18]=[CH:17][CH:16]=3)=[C:7]2[NH:14]1
Reactant: Nc1cccc(Oc2ccnc3[nH]c(=O)[nH]c23)c1
Reactant: O=C(Cl)c1cccc(C(F)(F)F)c1
Product: O=C(Nc1cccc(Oc2ccnc3[nH]c(=O)[nH]c23)c1)c1cccc(C(F)(F)F)c1
Yield: 32 %

Procedure:
Method H was used with 7-(3-aminophenoxy)-1H-imidazo[4,5-b]pyridin-2(3H)-one and 3-(trifluoromethyl)benzoyl chloride to afford the title compound as an off-white solid (17 mg, 32%). 1H-NMR (δ, ppm, DMSO-d6): 6.50 (d, 1H, HPy,5, J=6.0 Hz), 6.94 (d, 1H, Harom, J=8.0 Hz), 7.44 (ps t, 1H, Harom, J=8.0 Hz), 7.62 (s, 1H, Harom), 7.66 (d, 1H, Harom, J=7.5 Hz), 7.72-7.82 (m, 2H, Harom+Py,6), 7.96 (d, 1H, Harom, J=8.0 Hz), 8.24 (d, 1H, Harom, J=7.5 Hz), 8.26 (s, 1H, Harom), 10.55 (s, 1H, NHamide), 11.20 (s, 1H, NHPy3), 11.39 (s, 1H, NHPy2). 13C-NMR (δ, ppm, DMSO-d6): 106.62, 110.87, 113.79, 114.73, 116.37, 123.93, 124.26, 128.28, 129.19, 129.75, 130.25, 131.85, 135.54, 140.48, 141.35, 144.55, 147.17, 154.21, 154.78, 164.22. HRMS (EI): m/z [M+H] calcd for C20H14F3N4O3: 415.1018; found: 415.1010.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][CH:9]([OH:21])[C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([O:18][CH2:19]C)=[O:17])[CH:11]=2)[N:3]=1.[C:22]1([CH3:28])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Pd](Cl)Cl>[OH:21][CH:9]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([O:18][CH3:19])=[O:17])[CH:11]=1)[CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2](/[CH:4]=[CH:8]/[CH:9]([OH:21])[CH2:10][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:22][CH3:28])[N:3]=1
Reactant: Cc1ccccc1
Reactant: CCOC(=O)c1cccc(C(O)Cc2cccc(Br)n2)c1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Product: CCCCCCCCC(O)/C=C/c1cccc(CC(O)c2cccc(C(=O)OC)c2)n1
Temperature: 100 °C
Reaction time: 2 h

Procedure:
A solution of 120 mg of 2-bromo-6-[(2RS)-2-hydroxy-2-(3-ethoxycarbonylphenyl)-ethyl]-pyridine in 0.7 ml of toluene is mixed with 180 mg of (1E)-1-(tri-n-butylstannyl)-1-undecen-(3RS)-3-ol and 22 mg of 1,1'-bis-(diphenylphosphino)-ferrocene-palladium(II) chloride and stirred under argon atmosphere for 2 hours at 100° C. The reaction mixture is evaporated to dryness and the residue is chromatographed on silica gel with hexane/0-15% ethyl acetate. 56 mg of the title compound is obtained as oil.
Reaction SMILES: [Si:1]([O:8][CH:9]([CH2:12][OH:13])[CH2:10][OH:11])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[C:14](Cl)(=[O:32])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]/[CH:22]=[CH:23]\[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31]>N1C=CC=CC=1>[C:14]([O:11][CH2:10][CH:9]([CH2:12][O:13][C:14](=[O:32])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]/[CH:22]=[CH:23]\[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])(=[O:32])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]/[CH:22]=[CH:23]\[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31]
Reactant: CC(C)(C)[Si](C)(C)OC(CO)CO
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)Cl
Solvent: c1ccncc1
Product: CCCCCCCC/C=C\CCCCCCCC(=O)OCC(COC(=O)CCCCCCC/C=C\CCCCCCCC)O[Si](C)(C)C(C)(C)C
Reaction time: 15 h

Procedure:
In 60 ml of pyridine was dissolved 2.75 g (0.013 mol) of 2-O-(t-butyldimethylsilyl)glycerol, followed by addition of 8.82 g (0.028 mol) of oleoyl chloride under ice-cooling. The reaction was conducted at 50° C. for 15 hours. After completion of the reaction, the solvent was distilled off and the residue was diluted with methylene chloride, washed with saturated aqueous sodium hydrogen carbonate solution, dried, and concentrated. The above procedure provided 1,3-O-dioleoyl-2-O-(t-butyldimethylsilyl)glycerol.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[O:10][C:9](=[O:11])[NH:8][C:5]2=[N:6][CH:7]=1.[C:12]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])(=[O:15])[CH:13]=[CH2:14].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)C(C)C)(C)C>CN(C)C=O.C(#N)CC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:17]([O:16][C:12](=[O:15])/[CH:13]=[CH:14]/[C:2]1[CH:3]=[C:4]2[O:10][C:9](=[O:11])[NH:8][C:5]2=[N:6][CH:7]=1)([CH3:20])([CH3:19])[CH3:18]
Reactant: C=CC(=O)OC(C)(C)C
Reactant: O=c1[nH]c2ncc(Br)cc2o1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CCC#N
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)/C=C/c1cnc2[nH]c(=O)oc2c1
Yield: 23.2 %

Procedure:
A stirred solution of 6-bromo-3H-oxazolo[4,5-b]pyridin-2-one (1.00 g, 4.65 mmol), tert-butyl acrylate (2.7 mL, 18 mmol), palladium(II) acetate (104 mg, 0.465 mmol), tri-o-tolylphosphine (283 mg, 0.930 mmol), and N,N-diisopropylethylamine (1.7 mL, 9.7 mmol) in N,N-dimethylformamide (4 mL) and propionitrile (16 mL) was deoxygenated by bubbling argon through the solution for 20 min. The mixture was heated to reflux for 21 h, then allowed to cool. The mixture was concentrated in vacuo. The residue was dissolved in dichloromethane (100 mL). The solution was washed with water (2×200 mL), dried over sodium sulfate, filtered, and the solvent removed in vacuo to give a dark brown oil. Purification by flash column chromatography (silica gel, gradient from 98:2 to 94:6 CHCl3/MeOH) gave the title compound (283 mg, 23%) as a brown solid: 1H NMR (300 MHz, CDCl3) δ 8.24 (d, J=1.4 Hz, 1H), 7.64-7.55 (m, 2H), 6.37 (d, J=16.0 Hz, 1H), 1.55 (s, 9H).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]([O:12][CH3:13])=[O:11])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[OH-].[K+].[C:16]1([S:22](Cl)(=[O:24])=[O:23])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C(Cl)Cl>[CH3:13][O:12][C:10]([C:6]1[CH:5]=[C:4]2[C:9](=[CH:8][CH:7]=1)[N:1]([S:22]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)(=[O:24])=[O:23])[CH:2]=[CH:3]2)=[O:11]
Reactant: COC(=O)c1ccc2[nH]ccc2c1
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: [K+]
Agent: [OH-]
Solvent: ClCCl
Product: COC(=O)c1ccc2c(ccn2S(=O)(=O)c2ccccc2)c1
Reaction time: 0.33 h

Procedure:
After a suspension of methyl indole-5-carboxylate (1) (0.30 g, 1.71 mmol), TB AHS (0.19 g, 0.26 mmol) and KOH (0.19 g, 3.42 mmol) in CH2Cl2 (15 mL) was stirred for 20 min, benzenesulfonyl chloride (0.32 ml, 2.57 mmol) was added. The reaction mixture was stirred at room temperature overnight before it was quenched with water and extracted with CH2Cl2 (20 mL×3). The combined organic layer was dried over anhydrous MgSO4 and concentrated under reduced pressure to give a yellow residue.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:17]3[CH2:22][CH2:21][CH2:20][O:19][CH:18]=3)[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])=O.[NH4+]>>[C:1]([O:5][C:6]([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH:17]3[CH2:22][CH2:21][CH2:20][O:19][CH2:18]3)[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1Cc2ccc(C3=COCCC3)cc2C1
Agent: O=C[O-]
Agent: [NH4+]
Product: CC(C)(C)OC(=O)N1Cc2ccc(C3CCCOC3)cc2C1

Procedure:
Prepared in analogy to Example A49(b) from 5-(5,6-dihydro-4H-pyran-3-yl)-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester and ammonium formate. Light yellow oil. MS (m/e): 248.1 ([M+H−Me2C═CH2]+, 100%).
Reaction SMILES: I[CH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([C:9]2[N:10]=[N:11][N:12]3[C:17]=2[C:16]2[CH:18]=[CH:19][NH:20][C:15]=2[N:14]=[CH:13]3)[CH2:5][CH2:4]1.[F:21][C:22]([S:25]([O-:27])=[O:26])([F:24])[F:23].[Na+].O>CN(C)C=O>[F:21][C:22]([F:24])([F:23])[S:25]([CH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([C:9]2[N:10]=[N:11][N:12]3[C:17]=2[C:16]2[CH:18]=[CH:19][NH:20][C:15]=2[N:14]=[CH:13]3)[CH2:5][CH2:4]1)(=[O:27])=[O:26]
Reactant: O=S([O-])C(F)(F)F
Reactant: IC[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: O=S(=O)(C[C@H]1CC[C@H](c2nnn3cnc4[nH]ccc4c23)CC1)C(F)(F)F

Procedure:
1-[trans-4-(Iodomethyl)cyclohexyl]-7H-pyrrolo[3,2-e][1,2,3]triazolo[1,5-c]pyrimidine (50.0 mg, 0.131 mmol) and sodium trifluoromethylsulfinate (205 mg, 1.31 mmol) in N,N-dimethylformamide (3 mL) were stirred at 100° C. for 26 hours. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer washed with saturated aqueous sodium hydrogen carbonate, saturated aqueous ammonium chloride and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/2→1/1 (v/v)) and preparative HPLC (Waters XBridge Prep C18 μm ODS, 19×100 mm, acetonitrile/0.1% aqueous formic acid solution=20/80→80/20(v/v)) to give the title compound as a colorless solid (6.30 mg, yield 12%).
Reaction SMILES: [C:1]([CH2:9][CH2:10][C:11]([OH:13])=[O:12])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:21][C:22](O)([CH3:24])[CH3:23]>CN(C1C=CN=CC=1)C.C1C=CC=CC=1>[C:1]([CH2:9][CH2:10][C:11]([O:13][C:22]([CH3:24])([CH3:23])[CH3:21])=[O:12])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)O
Reactant: O=C(O)CCC(=O)c1ccccc1
Agent: CN(C)c1ccncc1
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)CCC(=O)c1ccccc1
Reaction time: 6 h
Yield: 64 %

Procedure:
Once the 3-benzoylpropionic acid had dissolved, then 6.1 mL (0.0830 mol) of triethylamine was added. The solution was stirred for 6 hours, after which the THF solution was filtered to remove the triethylamine hydrochloride. The filtrate was rotoevaporated to yield a light beige solid. To this solid was added 200 mL of benzene followed by 6.0 mL (0.104 mol) of 2-methyl-2-propanol and the mixture was stirred with heating to dissolve all of the solid. After complete dissolution, 5.40 g (0.0442 mol) of DMAP was added to the solution. The solution immediately turned dark red and was stirred at room temperature for 36 hours. The solution was washed with 10% aqueous HCl solution, followed by 2×5% aq. NaOH solution and finally with water. The organic layer was then dried (MgSO4), filtered and concentrated. The resultant oil was purified twice by column chromatography (silica gel, Eluent: 20% ethyl acetate: hexanes) and the resultant oil obtained was distilled under reduced pressure to yield 6.45 g (64%) of t-butyl 3-benzoylpropionate as a colorless oil. lit bp 129-130° C. at 1.5 mm Hg.; 1HNMR ppm (δ), CDCL3 7.98 (d, 2H), 7.54 (m, 1H), 7.46 (m, 2H), 3.26 (t, 2H), 2.68 (t, 2H), 1.45 (s, 9H). 13CNMR ppm (δ), CDCl3, 198.3 (C=O), 172.1 (CO2), 136.7 (q), 133.0, 128.6, 128.0, 80.6 (C(CH3)3), 33.5, 29.4, 28.0 (CH3).