Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[F:19][C:20]1[CH:60]=[CH:59][C:23]([CH2:24][C:25]2[S:29][C:28]([C:30]3[C:35]([Br:36])=[CH:34][N:33]=[C:32]([NH:37][CH2:38][CH2:39][N:40]4[C:44]([CH3:46])([CH3:45])[C:43](=[O:47])[NH:42][C:41]4=[O:48])[N:31]=3)=[CH:27][C:26]=2[CH2:49][CH2:50][O:51][Si](C(C)(C)C)(C)C)=[CH:22][CH:21]=1.O>O1CCCC1>[F:19][C:20]1[CH:60]=[CH:59][C:23]([CH2:24][C:25]2[S:29][C:28]([C:30]3[C:35]([Br:36])=[CH:34][N:33]=[C:32]([NH:37][CH2:38][CH2:39][N:40]4[C:44]([CH3:46])([CH3:45])[C:43](=[O:47])[NH:42][C:41]4=[O:48])[N:31]=3)=[CH:27][C:26]=2[CH2:49][CH2:50][OH:51])=[CH:22][CH:21]=1
Reactant: CC1(C)C(=O)NC(=O)N1CCNc1ncc(Br)c(-c2cc(CCO[Si](C)(C)C(C)(C)C)c(Cc3ccc(F)cc3)s2)n1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: O
Solvent: C1CCOC1
Product: CC1(C)C(=O)NC(=O)N1CCNc1ncc(Br)c(-c2cc(CCO)c(Cc3ccc(F)cc3)s2)n1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
Tetrabutylammonium fluoride (5 mL, 1M in tetrahydrofuran, 5.00 mmol) was added slowly to a solution of 1-(2-(4-(5-(4-fluorobenzyl)-4-(2-(tert-butyldimethylsilyloxy)ethyl)thiophen-2-yl)-5-bromopyrimidin-2-ylamino)ethyl)-5,5-dimethylimidazolidine-2,4-dione (1.8 g, 2.66 mmol) in tetrahydrofuran (40 mL) at rt. After stirring at rt for 4 h, 100 mL of water was added. The mixture was extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous sodium sulfate and filtered. The solvent was removed in vacuo and the product purified by flash chromatography eluting with methanol/dichloromethane (1:30) to give the title compound as a slightly yellow solid (1.2 g, 80%). MS (M+H)+ 562/564.
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[C:7]([CH3:9])[N:6]=[C:5](NC)[N:4]=1.[C:12](OC(=O)C)(=[O:14])C>[Zn]>[CH3:12][O:14][C:5]1[N:4]=[C:3]([O:2][CH3:1])[N:8]=[C:7]([CH3:9])[N:6]=1
Reactant: CC(=O)OC(C)=O
Reactant: CNc1nc(C)nc(OC)n1
Agent: [Zn]
Product: COc1nc(C)nc(OC)n1

Procedure:
Provided herein is a novel and useful process for preparing 2-methoxy-4-methyl-6-methylamino-1,3,5-triazine that broadly comprises the steps of (a) reacting zinc bis(imino-bis-carbimic acid methyl ester) with acetic anhydride to give 2,4-dimethoxy-6-methyl-1,3,5-triazine and (b) reacting the 2,4-dimethoxy-6-methyl-1,3,5-triazine, formed in step (a), with methylamine to give 2-methoxy-4-methyl-6-methylamino-1,3,5-triazine.
Reaction SMILES: C([O:5][C:6](=[O:28])[C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH2:18][CH2:17][N:16]([C:19](=[O:24])[C:20]([F:23])([F:22])[F:21])[CH2:15][CH2:14]2)=[CH:9][C:8]=1[N+:25]([O-:27])=[O:26])(C)(C)C>ClCCl>[N+:25]([C:8]1[CH:9]=[C:10]([N:13]2[CH2:18][CH2:17][N:16]([C:19](=[O:24])[C:20]([F:23])([F:22])[F:21])[CH2:15][CH2:14]2)[CH:11]=[CH:12][C:7]=1[C:6]([OH:28])=[O:5])([O-:27])=[O:26]
Reactant: CC(C)(C)OC(=O)c1ccc(N2CCN(C(=O)C(F)(F)F)CC2)cc1[N+](=O)[O-]
Solvent: ClCCl
Product: O=C(O)c1ccc(N2CCN(C(=O)C(F)(F)F)CC2)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 2-nitro-4-[4-(2,2,2-trifluoro-acetyl)-piperazin-1-yl]-benzoic acid tert-butyl ester (1.70 g, 4.22 mmol) in dichloromethane (25 mL) trifluoroacetic acid (5 mL) was added. The mixture was stirred at room temperature for 2 h, and then evaporated to give the title compound as yellow solid. 1H-NMR (400 MHz), δ (ppm, DMSO-d6): 13.21 (bs, 1H), 7.78 (d, J=8.9 Hz, 1H), 7.31 (d, J=2.5 Hz, 1H), 7.17 (dd, J1=8.9 Hz, J2=2.5 Hz, 1H), 3.74 (m, 4H), 3.56 (m, 4H).
Reaction SMILES: [SH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1.[H-].[Na+].CS(O[CH2:18][CH2:19][O:20][CH:21]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)(=O)=O>CN(C)C=O.O>[CH:21]1([O:20][CH2:19][CH2:18][S:1][C:2]2[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=2)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1
Reactant: CS(=O)(=O)OCCOC1CCCCCCC1
Reactant: CC(=O)c1ccc(S)cc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(=O)c1ccc(SCCOC2CCCCCCC2)cc1
Temperature: 60 °C
Reaction time: 0.33 h
Yield: 70.6 %

Procedure:
A stirred mixture of 1-(4-mercaptophenyl)ethanone (0.76 g) in dimethylformamide (10 mL) under argon was treated with 55% sodium hydride (0.218 g), stirred for 20 minutes and treated with 2-(cyclooctyloxy)ethyl methanesulfonate (1.25 g). The mixture was heated at 60° C. overnight, cooled, diluted with water, extracted twice with dichloromethane, and the organic layers were washed with water. The combined organic layers were dried (Na2SO4), filtered, and evaporated to give crude material which was purified by HPLC (dichloromethane-hexane-ethyl acetate; 48:48:4) to provide 1.08 g of 1-[4-[[2-(cyclooctyloxy)ethyl]thio]phenyl]ethanone as a colorless oil.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][NH:4][C:3]2[CH:7]=[N:8][CH:9]=[CH:10][C:2]1=2.[F:11][C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][C:20]=1[O:21][CH3:22])[C:15](Cl)=[O:16].C(N(CC)CC)C.Cl>ClCCl>[O:1]1[CH2:6][CH2:5][N:4]([C:15]([C:14]2[CH:18]=[CH:19][C:20]([O:21][CH3:22])=[C:12]([F:11])[CH:13]=2)=[O:16])[C:3]2[CH:7]=[N:8][CH:9]=[CH:10][C:2]1=2
Reactant: c1cc2c(cn1)NCCO2
Reactant: COc1ccc(C(=O)Cl)cc1F
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccc(C(=O)N2CCOc3ccncc32)cc1F
Temperature: 25 °C
Reaction time: 2 h
Yield: 33.1 %

Procedure:
In a 10 ml flask, 3,4-dihydro-2H-pyrido[4,3-b][1,4]oxazine (50 mg, 0.441 mmol) and 3-fluoro-4-methoxy-benzoyl chloride (125 mg, 0.661 mmol) were dissolved in dichloromethane. Triethylamine (0.77 ml, 1.288 mmol) was added thereto and then stirred at room temperature for 2 hours. After neutralizing with 1N hydrochloric acid solution, the mixture was extracted with dichloromethane and the combined organic layer was dried over anhydrous sodium sulfate (Na2SO4), filtered and evaporated under reduced pressure. The residue was purified by column chromatography on silica eluting with a solvent of ethyl acetate. The fractions containing the product were collected and evaporated to obtain white solid (42.1 mg, 33%).
Reaction SMILES: [C:1]([C:3]1[CH:23]=[CH:22][C:6]([CH2:7][C:8]2[C:9]([CH3:21])=[C:10]([CH3:20])[C:11]([CH:18]=C)=[C:12]([CH:17]=2)[C:13]([O:15][CH3:16])=[O:14])=[CH:5][C:4]=1[F:24])#[N:2].I([O-])(=O)(=O)=[O:26].[Na+].C(#N)C.O>CC(C)=O.[Os]=O>[C:1]([C:3]1[CH:23]=[CH:22][C:6]([CH2:7][C:8]2[C:9]([CH3:21])=[C:10]([CH3:20])[C:11]([CH:18]=[O:26])=[C:12]([CH:17]=2)[C:13]([O:15][CH3:16])=[O:14])=[CH:5][C:4]=1[F:24])#[N:2]
Reactant: C=Cc1c(C(=O)OC)cc(Cc2ccc(C#N)c(F)c2)c(C)c1C
Reactant: [O-][I+3]([O-])([O-])[O-]
Agent: O=[Os]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: O
Solvent: CC#N
Product: COC(=O)c1cc(Cc2ccc(C#N)c(F)c2)c(C)c(C)c1C=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 37.1 %

Procedure:
To a mixture of methyl 5-(4-cyano-3-fluorobenzyl)-3,4-dimethyl-2-vinylbenzoate (0.67 g) and sodium periodate (2.22 g) in acetone (15.0 mL)-acetonitrile (15.0 mL)-water (15.0 mL) was added osmium oxide (fixed catalyst I) (0.26 g), and the mixture was stirred overnight at room temperature under argon atmosphere. The reaction mixture was filtered, and the filtrate was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (0.25 g).
Reaction SMILES: F[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([NH:12][C:13](=[O:15])[CH3:14])=[C:4]([N+:16]([O-:18])=[O:17])[CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[OH:25][C:26]1[CH:33]=[CH:32][C:29]([CH:30]=[O:31])=[CH:28][CH:27]=1.O>CS(C)=O>[CH:30]([C:29]1[CH:32]=[CH:33][C:26]([O:25][C:2]2[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([NH:12][C:13](=[O:15])[CH3:14])=[C:4]([N+:16]([O-:18])=[O:17])[CH:3]=2)=[CH:27][CH:28]=1)=[O:31]
Reactant: O=Cc1ccc(O)cc1
Reactant: CC(=O)Nc1c([N+](=O)[O-])cc(F)cc1C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CS(C)=O
Product: CC(=O)Nc1c([N+](=O)[O-])cc(Oc2ccc(C=O)cc2)cc1C(F)(F)F
Yield: 44 %

Procedure:
A solution of N-[4-fluoro-2-nitro-6-(trifluoromethyl)phenyl]acetamide (1.5 g, 5.63 mmol), Cs2CO3 (4.59 g, 14.09 mmol), and 4-hydroxybenzaldehyde (0.757 g, 6.20 mmol) in dimethylsulfoxide (10 mL) was heated to 80 degrees Centigrade for 2 h and then cooled. H2O was added and the organics extracted using ethyl acetate (2×50 mL). The combined organics were then washed 1× brine and then dried (Na2SO4), filtered and concentrated. Chromatography on silica gel, using 2:1 hexanes/ethyl acetate eluted N-[4-[(4-formylphenyl)oxy]-2-nitro-6-(trifluoromethyl)phenyl]acetamide as an orange solid. (0.922 g; 44% yield).
Reaction SMILES: [Br:1][C:2]1[C:3]([CH3:11])=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.[C:12]([O:16][C:17]([N:19]1[CH2:22][CH:21]([CH2:23]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C(OCC)(=O)C>O1CCOCC1.O1CCCC1.O>[Br:1][C:2]1[CH:10]=[CH:9][C:8]2[C:4](=[CH:5][N:6]([CH2:23][CH:21]3[CH2:22][N:19]([C:17]([O:16][C:12]([CH3:13])([CH3:15])[CH3:14])=[O:18])[CH2:20]3)[N:7]=2)[C:3]=1[CH3:11]
Reactant: Cc1c(Br)ccc2[nH]ncc12
Reactant: Cc1ccc(S(=O)(=O)OCC2CN(C(=O)OC(C)(C)C)C2)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Solvent: O
Product: Cc1c(Br)ccc2nn(CC3CN(C(=O)OC(C)(C)C)C3)cc12
Temperature: 90 °C
Reaction time: 6 h

Procedure:
To a solution of 21.1 g of 5-bromo-4-methyl-1H-indazole and 37.6 g of tert-butyl-3-[(tosyloxy)-methyl]azetidin-1-carboxylate in 100 ml dioxan were added 150 ml of a 1M solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran at 25° C. and this was stirred for 6 hrs at 90° C. After cooling, the reaction mixture was treated with ethyl acetate and water, the organic phases separated and the aqueous phase extracted twice with 100 ml portions of ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulphate, and concentrated in vacuo after filtration.
Reaction SMILES: [CH2:1]([C:3]1[CH:4]=[C:5]([CH:10]=[C:11]([CH3:13])[N:12]=1)[C:6]([NH:8][OH:9])=[NH:7])[CH3:2].[CH2:14](OC(=O)C1C=C(C)N=C(C(C)C)C=1)C>>[OH:9][NH:8][C:6](=[NH:7])[C:5]1[CH:10]=[C:11]([CH3:13])[N:12]=[C:3]([CH:1]([CH3:14])[CH3:2])[CH:4]=1
Reactant: CCc1cc(C(=N)NO)cc(C)n1
Reactant: CCOC(=O)c1cc(C)nc(C(C)C)c1
Product: Cc1cc(C(=N)NO)cc(C(C)C)n1

Procedure:
The title compound is prepared in analogy to 2-ethyl-N-hydroxy-6-methyl-isonicotinamidine starting from 2-isopropyl-6-methyl-isonicotinic acid ethyl ester; LC-MS: tR=0.42 min, [M+1]+=194.08; 1H NMR (D6-DMSO): δ 1.22 (d, J=7.0 Hz, 6H), 2.44 (s, 3H), 2.91-3.02 (hept, J=7.0 Hz, 1H), 5.91 (s, 2H), 7.32 (s, 2H), 9.88 (s, 1H).
Reaction SMILES: [F:1][C:2]([F:24])([F:23])[C:3]1[CH:4]=[C:5]([C:9]2[N:19]3[C:20]4[N:12]([C:13](=[O:22])[NH:14][C:15](=[O:21])[C:16]=4[CH:17]=[N:18]3)[CH2:11][CH:10]=2)[CH:6]=[CH:7][CH:8]=1.[H-].[Na+].I[CH2:28][CH3:29]>CN(C)C=O.C(Cl)(Cl)Cl>[CH2:28]([N:14]1[C:13](=[O:22])[N:12]2[C:20]3[N:19]([C:9]([C:5]4[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:1])([F:23])[F:24])[CH:4]=4)=[CH:10][CH2:11]2)[N:18]=[CH:17][C:16]=3[C:15]1=[O:21])[CH3:29]
Reactant: CCI
Reactant: O=c1[nH]c(=O)n2c3c1cnn3C(c1cccc(C(F)(F)F)c1)=CC2
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClC(Cl)Cl
Product: CCn1c(=O)c2cnn3c2n(c1=O)CC=C3c1cccc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a stirred mixture of 5.0 g of 8-(3-(trifluoromethyl)phenyl)-3H,6H-1,4,5a,8a-tetraazaacenaphthylene-3,5(4H)-dione (prepared as described in Example 14) in 50 ml of dry N,N-dimethylformamide, under nitrogen, is added 800 mg of 60 percent sodium hydride (dispersion in mineral oil). The mixture is stirred at room temperature for 2 hours, then 10 ml of iodoethane is added and stirring is continued for 48 hours. The reaction mixture is evaporated to dryness, then treated with water, and the gummy solid which is isolated is dissolved in chloroform and the extract dried over anhydrous sodium sulfate. Evaporation gives an oil which is triturated with diethyl ether-hexane to provide a yellow solid which is collected by filtration to give 2.0 g of the desired product as a white solid. The product is recrystallized from isopropyl alcohol, mp 161-163° C.
Reaction SMILES: [Cl:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](Cl)=[O:5].[C:11]1([S:17]([N:20]2[CH:24]=[CH:23][CH:22]=[CH:21]2)(=[O:19])=[O:18])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Cl-].[Al+3].[Cl-].[Cl-]>ClC(Cl)C.C(OCC)(=O)C>[C:11]1([S:17]([N:20]2[CH:21]=[CH:22][CH:23]=[C:24]2[C:4]([C:3]2[C:2]([Cl:1])=[N:10][CH:9]=[CH:8][CH:7]=2)=[O:5])(=[O:19])=[O:18])[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: O=C(Cl)c1cccnc1Cl
Reactant: O=S(=O)(c1ccccc1)n1cccc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: CC(Cl)Cl
Solvent: CCOC(C)=O
Product: O=C(c1cccnc1Cl)c1cccn1S(=O)(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 49 %

Procedure:
To a solution of 2-chloro-nicotinoyl chloride (1.17 g) (Aldrich, Milwaukee, Wis.) and 1-benzensulfonyl-1H-pyrrole (1 g) (Aldrich) in dichloroethane (15 mL) was added aluminum chloride (1.1 g). After stirring at room temperature for one hour, the reaction was diluted with ethyl acetate, washed with water, base and brine, dried and purified to give 820 mg of (1-benzenesulfonyl-1H-pyrrol-2-yl)-(2-chloro-pyridin-3-yl)-methanone.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[CH2:7][CH2:6]2.[N-:13]=[N+]=[N-].[Na+].[OH-].[Na+].C([O-])(O)=O.[Na+]>CS(O)(=O)=O.C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:13][CH2:7][CH2:6]2
Reactant: COc1ccc2c(c1)CCC2=O
Reactant: [N-]=[N+]=[N-]
Agent: CS(=O)(=O)O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: COc1ccc2c(c1)CCNC2=O

Procedure:
5-Methoxy-1-indanone 1 (30 g, 185 mmol) is dissolved in CH3SO3H (96 mL) and CH2Cl2 (100 mL), NaN3 (24 g, 370 mmol) is then added in portions over a 1/2 hour period. After 2 hours the reaction mixture is cooled to 0° and is subsequently neutralized with 5N NaOH solution (200 mL) and saturated NaHCO3 solution. The resulting mixture is extracted with EtOAc (3×200 mL). The combined organic phases are washed with saturated NaCl solution (3×200 mL), dried over Na2SO4 and concentrated in vacuo. The resulting brown solid is washed with hexanes (2×100 mL) to give 6-methoxy-1-oxo-1,2,3,4-tetrahydroisoquinoline as a tan solid, m.p. 128°-130°.
Reaction SMILES: [CH3:1][CH:2]([CH2:4][CH2:5][CH2:6][C@H:7]([C@@H:9]1[C@:27]2([CH3:28])[C@H:12]([C@H:13]3[C@H:24]([CH2:25][CH2:26]2)[C@:22]2([CH3:23])[C:16]([CH2:17][C@H:18]([CH2:20][CH2:21]2)[OH:19])=[CH:15][CH2:14]3)[CH2:11][CH2:10]1)[CH3:8])[CH3:3].[C:29](O)(=[O:47])[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]/[CH:37]=[CH:38]\[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46].C(CC(C)(C)C)(C)C>CCOCC>[CH3:46][CH2:45][CH2:44][CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]/[CH:38]=[CH:37]\[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][C:29]([O:19][C@@H:18]1[CH2:17][C:16]2[C@@:22]([CH3:23])([C@@H:24]3[C@@H:13]([CH2:14][CH:15]=2)[C@@H:12]2[CH2:11][CH2:10][C@H:9]([C@@H:7]([CH2:6][CH2:5][CH2:4][CH:2]([CH3:1])[CH3:3])[CH3:8])[C@@:27]2([CH3:28])[CH2:26][CH2:25]3)[CH2:21][CH2:20]1)=[O:47]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Reactant: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C
Solvent: CC(C)CC(C)(C)C
Solvent: CCOCC
Product: CCCCCCCC/C=C\CCCCCCCC(=O)O[C@H]1CC[C@@]2(C)C(=CC[C@H]3[C@@H]4CC[C@H]([C@H](C)CCCC(C)C)[C@@]4(C)CC[C@@H]32)C1
Reaction time: 18 h

Procedure:
A mixture of 10 g of cholesterol, 22 g of oleic acid, 50 ml of isooctane and 200 ml (50,000 U) of an aqueous solution of lipase MY was stirred at 200 rpm for 18 hours. Thereafter, ether was added and the mixture was washed with aqueous sodium bicarbonate to remove the aqueous layer. After several repetitions of this procedure, the ether layer was dried on anhydrous sodium sulfate. The ether was then distilled off to give cholesteryl oleate, which was a white semi-transparent crude product, in 96.3% purity and in a yield of 16.0 g (95.0%).
Reaction SMILES: Br[CH:2]1[CH2:6][C:5](=[O:7])[C:4]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:3]1.[C:19]([OH:23])([CH3:22])([CH3:21])[CH3:20].OC1CC(=O)C(CCCCCCC(OCC)=O)=C1>C(=O)([O-])[O-].[Ag+2].CO>[C:19]([O:23][CH:2]1[CH2:6][C:5](=[O:7])[C:4]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:3]1)([CH3:22])([CH3:21])[CH3:20]
Reactant: CCOC(=O)CCCCCCC1=CC(Br)CC1=O
Reactant: CC(C)(C)O
Agent: [Ag+2]
Agent: CCOC(=O)CCCCCCC1=CC(O)CC1=O
Agent: O=C([O-])[O-]
Solvent: CO
Product: CCOC(=O)CCCCCCC1=CC(OC(C)(C)C)CC1=O

Procedure:
A stirred mixture of 6.35 g. (20 mmoles) of 4-bromo-2-(carbethoxyhexyl)cyclopent-2-en-1-one (Example 94), 3.01 g. (11 moles) of silver carbonate, and 40 ml. of t-butanol is heated at 70°C. for 17 hours. The mixture is cooled and filtered. After evaporation of t-butanol the residue is treated with aq. sodium chloride and extracted with 3:1 ether-hexane. The extract is washed with saturated sodium chloride solution, dried over magnesium sulfate, and concentrated. The crude product is purified by chromatography on silica gel to give, in order of elution: the subject compound as an oil; λ max.MeOH = 219 mμ (8860); ν max. = 1735 (ester carbonyl group), 1725 ketone carbonyl group), and 1365 cm-1 (tert.-butyl group); and 4-hydroxy-2-(6-carbethoxyhexyl)cyclopent-2-en-1-one also as an oil.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[CH:21][N:22]=3)[NH:17][N:16]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:24](I)[CH3:25].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[CH:21][N:22]=3)[N:17]([CH2:24][CH3:25])[N:16]=2)=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCI
Reactant: c1ccc(COc2ccc(-c3n[nH]c4nccnc34)cc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCn1nc(-c2ccc(OCc3ccccc3)cc2)c2nccnc21
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A suspension of 3-[4-(benzyloxy)phenyl]-1H-pyrazolo[3,4-b]pyrazine (0.58 g), EtI (0.18 ml), and K2CO3 (0.39 g) in DMF (5 mL) was stirred for 3 h at room temperature. The reaction mixture was poured into water and extracted with AcOEt. The extract was washed with water and brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (AcOEt/hexane) to give the title compound (0.61 g).
Reaction SMILES: Br[C:2]([CH3:17])([CH2:15][CH3:16])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]([Cl:13])[C:6]=1[Cl:14])=[O:4].[Br-].[Li+]>CN(C=O)C>[CH:15](=[C:2]([CH3:17])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]([Cl:13])[C:6]=1[Cl:14])=[O:4])[CH3:16]
Reactant: CCC(C)(Br)C(=O)c1ccc(OC)c(Cl)c1Cl
Agent: [Br-]
Agent: [Li+]
Solvent: CN(C)C=O
Product: CC=C(C)C(=O)c1ccc(OC)c(Cl)c1Cl

Procedure:
By following the procedure described in Example 5, Step C, using as the reactants 2-bromo-2-methyl-2',3'-dichloro-4'-methoxybutyrophenone (34 g., 0.1 mole), lithium bromide (17.4 g., 0.2 mole) and DMF (200 ml.), there is obtained 2-ethylidene-2',3'-dichloro-4'-methoxypropiophenone.
Reaction SMILES: Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[C:10]1(B(O)O)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.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:10]1([C:2]2[C:7]([C:8]#[N:9])=[CH:6][CH:5]=[CH:4][N:3]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: OB(O)c1ccccc1
Reactant: N#Cc1cccnc1Cl
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: N#Cc1cccnc1-c1ccccc1
Yield: 94.7 %

Procedure:
To a solution of 2-chloro-3-cyanopyridine (4.06 g, 29.3 mmol) in toluene (60 mL) was added phenylboronic acid (5.4 g, 43.9 mmol), potassium carbonate (6.1 g, 44.1 mmol) and tetrakis(triphenylphosphine)palladium (1.7 g, 1.5 mmol). The mixture was refluxed under nitrogen for 24 hours, then the solvent was removed under reduced pressure. The residue was purified on a silica gel column using 100% CH2Cl2 then 99:1 CH2Cl2:MeOH as mobile phase. Pure fractions were combined and dried in vacuo to yield the solid 2-phenyl-3 cyanopyridine (5.0 g, HPLC RT=2.98 min, method A; LC-MS m/z=181).
Reaction SMILES: [C:1]([C:5]1[C:10]([O:11][SiH:12]([CH3:14])[CH3:13])=[C:9]([Br:15])[C:8]([O:16][CH3:17])=[CH:7][C:6]=1[CH2:18][CH:19]1[C:24](=[O:25])[CH:23]=[CH:22][CH2:21][C:20]1([CH3:27])[CH3:26])([CH3:4])([CH3:3])[CH3:2]>C(OCC)(=O)C.[Pd]>[C:1]([C:5]1[C:10]([O:11][SiH:12]([CH3:13])[CH3:14])=[C:9]([Br:15])[C:8]([O:16][CH3:17])=[CH:7][C:6]=1[CH2:18][CH:19]1[C:20]([CH3:27])([CH3:26])[CH2:21][CH2:22][CH2:23][C:24]1=[O:25])([CH3:4])([CH3:2])[CH3:3]
Reactant: COc1cc(CC2C(=O)C=CCC2(C)C)c(C(C)(C)C)c(O[SiH](C)C)c1Br
Agent: [Pd]
Solvent: CCOC(C)=O
Product: COc1cc(CC2C(=O)CCCC2(C)C)c(C(C)(C)C)c(O[SiH](C)C)c1Br
Reaction time: 24 h
Yield: 75.4 %

Procedure:
To a flame-dried round-bottomed flask containing 6-[2'-(tert-butyl)dimethylsilyloxy-4'-bromo-5'-methoxyphenyl]methyl-5,5-dimethylcyclohex-2-en-1-one (13) (0.154 g, 0.454 mmol) in 22 mL ethyl acetate (which had been pre-dried over K2CO3) at room temperature was added 20 mg 5% palladium on carbon, and after flushing / evacuating the vessel 3 times with nitrogen, a hydrogen atmosphere was introduced and maintained by use of a balloon. After 24 h, the flask was again flushed several times with nitrogen, and the contents of the flask were filtered, rinsing with an additional 100 mL ethyl acetate. Rotary evaporation of the solvent afforded 0.156 g (quantitative) of the saturated benzylic ketone as a colorless, viscous oil (Rf 0.67, 2:1 hexanes/ethyl acetate). 1H NMR (400 MHz, CDCl3) δ0.22 and 0.25 [2s, 2×3H, Si(CH3)2 ], 0.87 and 1.12 (2s, 2×3H, geminal-CH3 's), 1.01 [s, 9H, SiC(CH3)3 ], 3.71 (s, 3H, OCH3), 6.79 (s, 1H, 6'-H), 6.91 ppm (s, 1H, 3'-H).
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]2[O:7][C:8]3[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=3[N:10]=2)[CH:3]=[N:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+].Br[CH2:24][CH2:25][C@@:26]([CH3:36])([S:32]([CH3:35])(=[O:34])=[O:33])[C:27]([O:29][CH2:30][CH3:31])=[O:28]>C(#N)C>[O:7]1[C:8]2[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=2[N:10]=[C:6]1[C:4]1[CH:5]=[N:1][N:2]([CH2:24][CH2:25][C@@:26]([CH3:36])([S:32]([CH3:35])(=[O:34])=[O:33])[C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:3]=1
Reactant: CCOC(=O)[C@@](C)(CCBr)S(C)(=O)=O
Reactant: c1ccc2oc(-c3cn[nH]c3)nc2c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Agent: [I-]
Solvent: CC#N
Product: CCOC(=O)[C@@](C)(CCn1cc(-c2nc3ccccc3o2)cn1)S(C)(=O)=O
Temperature: 50 °C
Yield: 91.2 %

Procedure:
To a solution of 2-(1H-pyrazol-4-yl)-1,3-benzoxazole (0.250 g, 1.35 mmol) in acetonitrile (10 mL) was added cesium carbonate (1.10 g, 3.38 mmol, 2.5 eq), sodium iodide (0.041 g, 0.270 mmol, 0.2 eq) and (R)-ethyl 4-bromo-2-methyl-2-(methylsulfonyl)butanoate (0.504 g, 1.76 mmol, 1.3 eq). The mixture was heated at 50° C. overnight. The reaction mixture was filtered over a pad of diatomateous earth. The filtrate was evaporated and the crude was purified by flash chromatography on silica gel eluting with 10-100% ethyl acetate/heptane to give ethyl (2R)-4-[4-(1,3-benzoxazol-2-yl)-1H-pyrazol-1-yl]-2-methyl-2-(methylsulfonyl)butanoate (0.482 g, 91% yield) as a white solid. LC-MS M+H+392.1.