Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]([C:8]1[CH:13]=[CH:12][C:11]([CH2:14][C:15](C2C=CC=CC=2)=O)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([C:27]#[N:28])(C)C.[ClH:29]>C(Cl)Cl.[I-].[Mg+2].[I-]>[Cl:29][C:14]([C:11]1[CH:10]=[CH:9][C:8]([O:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:13][CH:12]=1)([CH3:15])[C:27]#[N:28]
Reactant: O=C(Cc1ccc(Oc2ccccc2)cc1)c1ccccc1
Reactant: C[Si](C)(C)C#N
Reactant: Cl
Agent: [I-]
Agent: [Mg+2]
Solvent: ClCCl
Product: CC(Cl)(C#N)c1ccc(Oc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
A mixture of 4-phenoxyphenylacetophenone (6.36 g), trimethylsilylcyanide (3.96 g) and magnesium iodide (10 mg) in methylene chloride (30 ml) was stirred for 12 hrs at room temperature, 156 hydrochloric acid (10 ml) was then added. The mixture was again stirred for 8 hrs at room temperature. The organic layer was separated and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure. The residue was dissolved in benzene (50 ml) and pyridine (2.37 g) and thionyl chloride (4.76 g) were added at 0° C. with stirring. The reaction mixture was stirred for an additional 3 hrs at room temperature and then the solvent was evaporated. The residue was purified by column chromatography to give 7.09 g of 2-chloro-2-(4-phenoxyphenyl)propionitrile as an oil.
Reaction SMILES: [S:1]([O-:4])([O-:3])=[O:2].[Na+:5].[Na+:6].Cl[CH:8]([C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:22][CH3:23])[CH:18]=2)[CH:13]=1)[C:9]([OH:11])=[O:10].[Na]>C(O)C>[S:1]([CH:8]([C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:22][CH3:23])[CH:18]=2)[CH:13]=1)[C:9]([OH:11])=[O:10])([OH:4])(=[O:3])=[O:2].[Na:5][Na:6]
Reactant: [Na+]
Reactant: O=S([O-])[O-]
Reactant: COc1ccc2cc(C(Cl)C(=O)O)ccc2c1
Agent: [Na]
Solvent: CCO
Product: COc1ccc2cc(C(C(=O)O)S(=O)(=O)O)ccc2c1
Product: [Na][Na]
Reaction time: 15 h

Procedure:
To a solution of 250 ml. of anhydrous ethanol and 0.12 moles of sodium sulfite is added 0.1 moles α-chloro-6-methoxy-2-naphthylacetic acid, sodium salt. The reaction mixture is stirred for 15 hours, filtered and the residue worked with ethanol. The filtrate is evaporated to dryness to obtain α-sulfo-6-methoxy-2-naphthylacetic acid, disodium salt.
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([OH:12])=[C:4]([C:13]([OH:15])=O)[N:3]=1.F[P-](F)(F)(F)(F)F.N1([O+]=C(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[CH3:40][O:41][CH2:42][CH2:43][NH2:44].C(N(C(C)C)C(C)C)C>ClCCl>[CH3:40][O:41][CH2:42][CH2:43][NH:44][C:13]([C:4]1[N:3]=[C:2]([Cl:1])[C:11]2[C:6]([C:5]=1[OH:12])=[CH:7][CH:8]=[CH:9][CH:10]=2)=[O:15]
Reactant: O=C(O)c1nc(Cl)c2ccccc2c1O
Reactant: COCCN
Agent: CN(C)C(=[O+]n1nnc2ccccc21)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COCCNC(=O)c1nc(Cl)c2ccccc2c1O
Reaction time: 288 h
Yield: 15.7 %

Procedure:
To a mixture of 45 mg (0.2 mmol) of 1-chloro-4-hydroxy-isoquinoline-3-carboxylic acid (from example A-1 d), 76 mg (0.2 mmol) of benzotriazol-1-yl-(bis-dimethylamino-methylene)-oxonium hexafluoro phosphate (HBTU), 18 μl 2-methoxy-ethylamine (0.2 mmol), and 1 ml of dichloromethane were added 96 μl (0.55 mmol) of ethyl-diisopropyl-amine with stirring. Stirring was continued at ambient temperature for 12 days. The product was isolated from the reaction mixture by flash column chromatography on silica gel using hexanes:ethyl acetate (9:1) as the eluent to give a white solid. 8.8 mg of the title compound were obtained; MS-(+)-ion: M+1=281.0.
Reaction SMILES: [CH3:1][C:2]1([CH3:11])[O:7][CH2:6][C:5]([CH2:9][OH:10])([CH3:8])[CH2:4][O:3]1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C)C=CC=CC=1.[CH2:29]([O:36][CH2:37][CH2:38]OS(C(F)(F)F)(=O)=O)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>O1CCCC1.ClCCl>[CH3:1][C:2]1([CH3:11])[O:3][CH2:4][C:5]([CH2:9][O:10][CH2:38][CH2:37][O:36][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)([CH3:8])[CH2:6][O:7]1
Reactant: O=S(=O)(OCCOCc1ccccc1)C(F)(F)F
Reactant: CC1(CO)COC(C)(C)OC1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: CC1(COCCOCc2ccccc2)COC(C)(C)OC1
Temperature: -20 °C
Reaction time: 1 h
Yield: 100 %

Procedure:
A solution of 2,2-dimethyl-5-hydroxymethyl-5-methyl-1,3-dioxane (13.4 g, 0.084 mol) in 630 mL of anhydrous tetrahydrofuran was cooled to -20° C. under argon atmosphere. Then a 0.5M solution of potassium bis(trimethylsilyl)amide in toluene (168 mL, 0.084 mol) was added and the mixture was stirred at -20° C. for 1 hr. The 2-benzyloxyethyltriflate (23.8 g, 0.084 mol) was added neat, keeping the temperature between -20° and -15° C. The resulting solution was stirred at this temperature for 1 hr, then gradually allowed to warm to 25° C. and stirred for 15 hrs. Dichloromethane (900 mL) was added and the solution was washed twice with 300 mL of water and once with 100 mL of saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate and evaporation of the solvents under reduced pressure gave 2,2-dimethyl-5-benzyloxyethoxymethyl-5-methyl-1,3-dioxane (24.6 g, 0.084 mol, 100%) which was not purified.
Reaction SMILES: Cl.[C:2]([C:7]1[N:8]=[C:9]([C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)[NH:10][C:11]=1[NH2:12])([O:4][CH2:5][CH3:6])=[O:3].[N:19]([O-])=O.[Na+].[CH3:23][NH:24][CH3:25].C(=O)([O-])[O-].[Na+].[Na+]>Cl.O>[C:2]([C:7]1[N:8]=[C:9]([C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)[NH:10][C:11]=1[N:12]=[N:19][N:24]([CH3:25])[CH3:23])([O:4][CH2:5][CH3:6])=[O:3]
Reactant: CNC
Reactant: O=N[O-]
Reactant: CCOC(=O)c1nc(-c2cccnc2)[nH]c1N
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Product: CCOC(=O)c1nc(-c2cccnc2)[nH]c1N=NN(C)C
Temperature: 25 °C

Procedure:
4-Carbethoxy-5-amino-2-(3-pyridyl)imidazole hydrochloride (1.90 gm) was dissolved in 5N hydrochloric acid (10 mls) and the mixture stirred at room temperature. A solution of sodium nitrite (0.5 gm) in water (5 ml) was then added in small portions, and the resulting clear solution stirred for 5 minutes. The mixture was then poured into a vigorously stirred mixture of 30% aqueous dimethylamine (1.0 ml) and 10% aqueous sodium carbonate (20 mls) giving a pale brown precipitate. The crude product was recrystallized from methanol/ether to give 0.65 gm of an off-white solid mp. 125° with decomposition.
Reaction SMILES: [F:1][C:2]([F:21])([F:20])[C:3](OS(C)(=O)=O)([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][O:13][CH3:14])=[CH:7][N:6]=1)[CH3:4].[CH3:22][Al](C)C.O>ClCCl>[CH3:14][O:13][CH2:12][O:11][C:8]1[CH:9]=[CH:10][C:5]([C:3]([CH3:22])([CH3:4])[C:2]([F:21])([F:20])[F:1])=[N:6][CH:7]=1
Reactant: C[Al](C)C
Reactant: COCOc1ccc(C(C)(OS(C)(=O)=O)C(F)(F)F)nc1
Solvent: ClCCl
Solvent: O
Product: COCOc1ccc(C(C)(C)C(F)(F)F)nc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 53.4 %

Procedure:
1.7 g (4.13 mmol) methanesulfonic acid 2,2,2-trifluoro-1-(5-methoxymethoxy-pyridin-2-yl)-1-methyl-ethyl ester was dissolved in 20 ml dichloromethane. The reaction mixture was cooled to 0° C. where 2.065 ml (4.13 mmol) trimethylaluminum was added slowly. The reaction mixture was stirred at room temperature for 20 h. After that water was added slowly and the mixture was extracted 2 times with EtOAc. The combined organic layers were washed with water and brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by chromatography on silicagel (EtOAc, heptane) to yield to afford 0.55 g of the pure title compound. LCMS (method L): tR=1.09 min, M+H=250.
Reaction SMILES: [F:1][C:2]1([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH:7]([O:8]C(=O)C)[NH:6][C:5](=[O:12])[NH:4][C:3]1=[O:13].[CH3:19][C:20]1[O:27][C:23](/[CH:24]=[N:25]/O)=[CH:22][CH:21]=1.C(N(CC)CC)C.O>N1C=CC=CC=1>[F:1][C:2]1([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH:7]([O:8]/[N:25]=[CH:24]/[C:23]2[O:27][C:20]([CH3:19])=[CH:21][CH:22]=2)[NH:6][C:5](=[O:12])[NH:4][C:3]1=[O:13]
Reactant: CCOC(=O)C1(F)C(=O)NC(=O)NC1OC(C)=O
Reactant: Cc1ccc(/C=N/O)o1
Solvent: c1ccncc1
Solvent: CCN(CC)CC
Solvent: O
Product: CCOC(=O)C1(F)C(=O)NC(=O)NC1O/N=C/c1ccc(C)o1
Temperature: 25 °C
Reaction time: 15 h
Yield: 51.5 %

Procedure:
In 70 ml of pyridine were dissolved 18.3 g (70 mmol) of ethyl 5-fluoro-6-acetoxy-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate and 13.1 g (105 mmol) of (E)-5-methylfurfuraldoxime (containing 13% of the Z form), and 7.07 g (70 mmol) of triethylamine was added to the solution, followed by stirring at room temperature for 15 hours. The reaction solution was poured into 500 ml of ice-cooled water, and crystals precipitated were collected by filtration and washed with water. The crystals were dried under reduced pressure (P2O5) and recrystallized from 170 ml of ethanol to give 11.8 g of ethyl 5-fluoro-6-[(E)-5-methylfurfurylideneaminooxy]-1,2,3,4,5,6-hexahydro-2,4-dioxopyrimidine-5-carboxylate. m.p. 181°-182° C.
Reaction SMILES: [CH3:1][C:2]([CH3:6])=[CH:3][CH2:4][Br:5].[C:7]1([P:13]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>C1(C)C=CC=CC=1>[Br-:5].[CH3:1][C:2]([CH3:6])=[CH:3][CH2:4][P+:13]([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1
Reactant: CC(C)=CCBr
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: CC(C)=CC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Product: [Br-]
Reaction time: 18 h

Procedure:
A mixture of 3,3-dimethylallyl bromide (50.0 g), triphenylphosphine (88.0 g) and dry toluene (500 ml) was stirred and heated at the reflux temperature for one hour, and then kept at the ambient temperature for 18 hours. The white precipitate of 3,3-dimethylallyl triphenylphosphonium bromide (m.p. 242°0 C.) was collected by filtration, washed with diethyl ether and dried.
Reaction SMILES: [OH-].[K+].[NH2:3][C@H:4]([C:12]([OH:14])=[O:13])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[CH:15]([NH:17][C@@H:18]1[C:23](=[O:24])[O:22][C:20](=[O:21])[CH2:19]1)=[O:16].[OH-].[Na+]>O>[CH:15]([NH:17][C@H:18]([C:23]([NH:3][C@H:4]([C:12]([OH:14])=[O:13])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:24])[CH2:19][C:20](=[O:21])[OH:22])=[O:16].[CH:15]([NH:17][C@H:18]([C:23]([OH:24])=[O:22])[CH2:19][C:20]([NH:3][C@H:4]([C:12]([OH:14])=[O:13])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:21])=[O:16]
Reactant: N[C@@H](Cc1ccccc1)C(=O)O
Reactant: O=CN[C@H]1CC(=O)OC1=O
Agent: [K+]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=CN[C@@H](CC(=O)N[C@@H](Cc1ccccc1)C(=O)O)C(=O)O
Product: O=CN[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1ccccc1)C(=O)O
Temperature: -5 °C
Reaction time: 1 h

Procedure:
To an aqueous solution containing 13.2 g of potassium hydroxide dissolved in 330 ml of water was added 33.0 g (0.20 mole) of L-phenylalanine to form a solution. After being cooled to -5° C., the solution was fed little by little with 30.0 g (0.21 mole) of N-formyl-L-aspartic acid anhydride for one hour while maintaining its temperature at -5° C. to 5° C. A 10% aqueous sodium hydroxide solution was added thereto simultaneously to maintain the reaction liquid at a pH of 8-11. Thereafter, the reaction was carried out at the same temperature for one hour. The reaction mixture was analyzed by high speed liquid chromatography, with the result that the isomer formation ratio of N-formyl-α-L-aspartyl-L-phenylalanine to N-formyl-β- L-aspartyl-L-phenylalanine was 78:22 while the overall yield was 98% based on L-phenylalanine.
Reaction SMILES: [C:1]1([CH:7]([N:9]2[CH2:12][CH:11](O)[CH2:10]2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C-:14]#[N:15].[K+].CO.[C:19]([OH:26])(=[O:25])/[CH:20]=[CH:21]\[C:22]([OH:24])=[O:23]>CC(O)C>[C:19]([OH:26])(=[O:25])/[CH:20]=[CH:21]\[C:22]([OH:24])=[O:23].[C:1]1([CH:7]([N:9]2[CH2:12][CH:11]([C:14]#[N:15])[CH2:10]2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: [C-]#N
Reactant: CC(c1ccccc1)N1CC(O)C1
Agent: O=C(O)/C=C\C(=O)O
Agent: [K+]
Solvent: CC(C)O
Solvent: CO
Product: CC(c1ccccc1)N1CC(C#N)C1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
A slurry of methanesulfonate ester of 1-(1-phenylethyl)azetidin-3-ol (60.4 g, 223 mmol), potassium cyanide (43.5 g, 669 mmol) and methanol (350 mol) were allowed to stir at ambient temperature for 72 h. The reaction mixture was filtered and the filtrate was concentrated in vacuo. The residue was partitioned between 300 mL of an aqueous 20% potassium carbonate solution and 400 mL of diethyl ether. The organic layer was separated, dried (MgSO4) and concentrated in vacuo. The residue was chromatographed (SiO2, flash, ethyl acetate/hexane 1:3) to give 25.1 g (56%). A 1-g portion was dissolved in 2-propanol and treated with maleic acid (0.75 g, 6.5 mmol). The resulting solid was recrystallized from 2-propanol to give a white solid, mp 147°-148° C.
Reaction SMILES: FC1C([O:8][C:9](=O)[C@H:10]([CH2:29][CH2:30][CH2:31][CH2:32][NH:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[NH:11][C:12]([O:14][CH2:15][CH:16]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]3[C:17]2=[CH:18][CH:19]=[CH:20][CH:21]=3)=[O:13])=C(F)C(F)=C(F)C=1F.[N+:46]([O:49][CH2:50][CH2:51][CH2:52][CH2:53][OH:54])([O-:48])=[O:47]>CN(C=O)C>[CH:18]1[C:17]2[CH:16]([CH2:15][O:14][C:12](=[O:13])[NH:11][C@H:10]([C:9]([O:54][CH2:53][CH2:52][CH2:51][CH2:50][O:49][N+:46]([O-:48])=[O:47])=[O:8])[CH2:29][CH2:30][CH2:31][CH2:32][NH:33][C:34](=[O:35])[O:36][C:37]([CH3:38])([CH3:39])[CH3:40])[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]=2[CH:21]=[CH:20][CH:19]=1
Reactant: CC(C)(C)OC(=O)NCCCC[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)Oc1c(F)c(F)c(F)c(F)c1F
Reactant: O=[N+]([O-])OCCCCO
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)NCCCC[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)OCCCCO[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 4 h

Procedure:
Commercial N(α)-Fmoc-N(ε)-Boc-L-lysine pentafluorophenyl ester (6.51 mmol) and 4-(nitrooxy)-1-butanol (6.55 mmol) were dissolved in DMF (12 ml) and the mixture was cooled to 0° C. N,N-dimethylaminopyridine (DMAP) (6.55 mmol) were added and the reaction was slowly warmed to room temperature and stirred for 4 hours. Then the mixture was concentrate under reduced pressure and diluted with EtOAc, washed with 5% aqueous Na2HPO4 and brine.
Reaction SMILES: [H-].[Na+].[C:3]1([OH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[I:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[N:17]=[CH:16][N:15]=[C:14]2Cl>CN(C=O)C>[I:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[N:17]=[CH:16][N:15]=[C:14]2[O:9][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: Clc1ncnc2ccc(I)cc12
Reactant: Oc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Ic1ccc2ncnc(Oc3ccccc3)c2c1
Temperature: 0 °C
Reaction time: 2 h
Yield: 98.2 %

Procedure:
A suspension of NaH (washed free of mineral oil) in DMF (40 mL) was cooled to 0° C. and a solution of phenol (5.65 g, 60 mmol) in DMF (20 mL) was added dropwise. Upon completion of addition, 6-iodo-4-chloroquinazoline 13 (14.6 g, 50.3 mmol) was added as a solid in small portions. The cooling bath was moved and the reaction mixture was stirred at room temperature for 2 hours. The mixture was then quenched with water (200 mL), diluted with EtOAc (300 mL) and transferred to a separatory funnel. The organic layer was washed with dilute aqueous NaOH, water and brine and dried over Na2SO4. Filtration of the solids and removal of the solvent provided 6-iodo-4-phenoxyquinazoline 14 (17.2 g, 98%) as a yellow solid. 1H NMR (400 MHz; CDCl3): δ: 8.74 (d, 1H), 8.14 (s, 1H), 8.12 (dd, 1H), 7.71 (d, 1H), 7.49 (dd, 2H), 7.32 (t, 1H), 7.22 (m, 2H).
Reaction SMILES: [P:1]([O:8]CC)([O:5][CH2:6][CH3:7])[O:2][CH2:3][CH3:4].[OH2:11].[CH2:12](N(CC)CC)C>>[OH:11][CH2:12][P:1](=[O:8])([O:5][CH2:6][CH3:7])[O:2][CH2:3][CH3:4]
Reactant: CCN(CC)CC
Reactant: CCOP(OCC)OCC
Reactant: O
Product: CCOP(=O)(CO)OCC

Procedure:
Reaction Procedure Incorporating Triethyl Phosphite as an Acid/Water Reducer and Using Triethylamine as the Amine Catalyst (Extreme Exotherm)
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1C[O:14]CC1.[Br:16][C:17]1[CH:18]=[C:19]([C:23]2[CH:38]=[C:26]3[N:27]=[C:28]([CH3:37])[C:29]([CH2:32][C:33]([O:35][CH3:36])=[O:34])=[C:30]([I:31])[N:25]3[N:24]=2)[CH:20]=[CH:21][CH:22]=1.C1(C2ON2S(C2C=CC=CC=2)(=O)=O)C=CC=CC=1>C1COCC1>[Br:16][C:17]1[CH:18]=[C:19]([C:23]2[CH:38]=[C:26]3[N:27]=[C:28]([CH3:37])[C:29]([CH:32]([OH:14])[C:33]([O:35][CH3:36])=[O:34])=[C:30]([I:31])[N:25]3[N:24]=2)[CH:20]=[CH:21][CH:22]=1
Reactant: C1CCOC1
Reactant: COC(=O)Cc1c(C)nc2cc(-c3cccc(Br)c3)nn2c1I
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: O=S(=O)(c1ccccc1)N1OC1c1ccccc1
Agent: [K+]
Product: COC(=O)C(O)c1c(C)nc2cc(-c3cccc(Br)c3)nn2c1I
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 67.6 %

Procedure:
To a stirred solution of 0.9M KHMDS/THF (2.55 mL, 2.297 mmol) in THF (8 mL) at −78° C. was added dropwise a THF (10 mL) solution of methyl 2-(2-(3-bromophenyl)-7-iodo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (859 mg, 1.767 mmol) over 5 min. After 30 min, a THF (10 mL) solution of 3-phenyl-2-(phenylsulfonyl)-1,2-oxaziridine (600 mg, 2.297 mmol) was added to the resulting red reaction mixture and stirred for additional 30 min at −78° C. Then, the resulting orange reaction mixture was quenched with sat. NH4Cl (50 mL), diluted with EtOAc (200 mL), washed with water (100 mL), brine (100 mL), dried (Na2SO4), filtered and concentrated to give light solid. This solid was triturated with small amount of ethyl acetate and solids were filtered, washed with hexanes and dried under high vacuo to afford methyl 2-(2-(3-bromophenyl)-7-iodo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate (600 mg, 1.195 mmol, 67.6% yield) as light yellow solid. 1H NMR (500 MHz, CDCl3) δ: 8.21 (t, J=1.7 Hz, 1H), 7.96 (dt, J=7.8, 1.2 Hz, 1H), 7.59-7.55 (m, 1H), 7.37 (t, J=7.8 Hz, 1H), 7.09 (s, 1H), 5.78 (s, 1H), 3.87 (s, 3H), 3.54 (br. s., 1H), 2.61 (s, 3H). LCMS (M+H)=504.05.
Reaction SMILES: [CH3:1][CH2:2][O:3][C:4]([CH:6]1[C:10](=[O:11])[CH2:9][CH2:8][CH2:7]1)=[O:5].[C:12]1([C:14](=[CH:16][CH:17]=[CH:18][CH:19]=1)O)[OH:13].C1(C)C=CC(S(O)(=O)=O)=CC=1.C1C=CC=CC=1>O>[C:10]12([O:13][C:12]3[CH:14]=[CH:16][CH:17]=[CH:18][C:19]=3[O:11]1)[CH2:9][CH2:8][CH2:7][CH:6]2[C:4]([O:3][CH2:2][CH3:1])=[O:5]
Reactant: Oc1ccccc1O
Reactant: CCOC(=O)C1CCCC1=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccccc1
Solvent: O
Product: CCOC(=O)C1CCCC12Oc1ccccc1O2

Procedure:
A mixture of 15.7 g. of ethyl cyclopentanone-2-carboxylate, 11 g. of pyrocatechol, 0.5 g. of p-toluenesulphochloride and 0.5g. of p-toluenesulphonic acid in 100 cc. of anhydrous benzene is refluxed until the theoretical amount of water no longer distils azeotropically. The mixture is washed first with dilute NaOH and then with H2O until neutral. After drying with Na2SO4 the solvent is removed under vacuum. The residual oil is fractionated, and the desired product boils at 136°-139°C./0.3 mm.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([C:14]#[N:15])=[CH:10][NH:11][C:12]=2[CH3:13])=[C:4]([C:16](=O)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[Cl:23])[CH:3]=1>[Ni].C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]2[C:8]3[C:9](=[CH:10][NH:11][C:12]=3[CH3:13])[CH2:14][N:15]=[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[Cl:23])[C:4]=2[CH:3]=1
Reactant: Cc1[nH]cc(C#N)c1-c1ccc(Cl)cc1C(=O)c1ccccc1Cl
Agent: [Ni]
Solvent: CC(=O)O
Product: Cc1[nH]cc2c1-c1ccc(Cl)cc1C(c1ccccc1Cl)=NC2

Procedure:
A mixture of 8.5 g (24 mmol) of 4-[4-chloro-2-(2-chlorobenzoyl)phenyl]-5-methyl-1H-pyrrole-3-carbonitrile, 1 spoonful of Raney nickel and 250 ml of glacial acetic acid was hydrogenated on a Parr apparatus at 55 psi overnight. The catalyst was removed by filtration and the acetic acid was removed at reduced pressure. The residue was diluted with water, basified with concentrated ammonium hydroxide and the resulting precipitate was collected by filtration. The precipitate was dissolved in tetrahydrofuran, dried over anhydrous sodium sulfate and concentrated at reduced pressure. The residue was crystallized from a mixture of ether and petroleum ether to give off-white crystals (mp 219°-222°). Recrystallization from a mixture of ether and methylene chloride gave colorless crystals, mp 221°-225°.
Reaction SMILES: F[B-](F)(F)F.[CH3:6][O+:7]([CH3:9])C.[CH2:10]([CH:13]1[CH2:17][NH:16]C(=O)[CH2:14]1)[CH2:11][CH3:12].C(=O)([O-])O.[Na+]>C(Cl)Cl>[CH3:6][O:7][C:9]1[CH2:14][CH:13]([CH2:10][CH2:11][CH3:12])[CH2:17][N:16]=1
Reactant: CCCC1CNC(=O)C1
Reactant: C[O+](C)C
Agent: F[B-](F)(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CCCC1CN=C(OC)C1
Temperature: 25 °C
Reaction time: 14 h
Yield: 67.3 %

Procedure:
Trimethyloxonium tetrafluoroborate (715 mg, 4.83 mmol) was added to a solution of 4-propyl-2-pyrrolidinone (410 mg, 3.22 mmol) in methylene chloride (8 ml) and the mixture was stirred at room temperature for 14 hours. Saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture to render it weekly basic and then it was extracted with ethyl acetate. After washing the organic layer with brine and drying over anhydrous magnesium sulfate, the organic layer was subjected to distillation under reduced pressure. The residue was purified by silica gel column chromatography (solvent: n-hexane-ethyl acetate) to yield the title compound (306 mg) as a light yellow oil. 1H-NMR (CDCl3) δ(ppm) 0.90 (3H, t, J=7.2 Hz), 1.21-1.50 (4H, m), 2.13 (1H, dd, J=16.4 Hz, 16.8 Hz), 2.34-2.48 (1H, m), 2.57 (1H, dd, J=16.4 Hz, 9.2 Hz), 3.24 (1H, dd, J=13.6 Hz, 6.0 Hz), 3.71-3.90 (4H, m)
Reaction SMILES: [CH3:1][C:2]([CH3:16])([CH3:15])[CH2:3][CH2:4][C:5]([C:7]1[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][CH:8]=1)=[O:6].[CH2:17](O)[CH2:18][OH:19].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.CCOC(C)=O>[CH3:1][C:2]([CH3:16])([CH3:15])[CH2:3][CH2:4][C:5]1([C:7]2[CH:8]=[CH:9][C:10]([C:11]#[N:12])=[CH:13][CH:14]=2)[O:19][CH2:18][CH2:17][O:6]1
Reactant: OCCO
Reactant: CC(C)(C)CCC(=O)c1ccc(C#N)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Solvent: O
Product: CC(C)(C)CCC1(c2ccc(C#N)cc2)OCCO1
Temperature: 135 °C
Yield: 81.9 %

Procedure:
Dissolve 4-(4,4-dimethyl-pentanoyl)-benzonitrile (275 mg, 1.28 mmol) in toluene (10 mL). Add ethylene glycol (0.35 mL, 6.4 mmol) and p-toluenesulfonic acid monohydrate (24 mg, 0.128 mmol). Heat the mixture at 135° C. in a Dean-Stark for 2 h and then at 120° C. overnight. Cool the mixture to room temperature, dilute with EtOAc and wash with saturated aqueous NaHCO3. Dry the organic phase over MgSO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on basic alumina eluting with hexane and hexane/EtOAc (19:1) to give the desired intermediate as an oil (0.272 g, 82%).
Reaction SMILES: [C:1](OO)(=O)[CH3:2].[C:6]([O:14][CH:15]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)C(=O)C1C=CC=CC=1)(=[O:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[C:30]([O-:33])([O-])=[O:31].[Na+].[Na+]>ClCCl>[C:30]([O:33][CH:15]([O:14][C:6](=[O:13])[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)(=[O:31])[C:2]1[CH:1]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: O=C([O-])[O-]
Reactant: O=C(OC(C(=O)c1ccccc1)c1ccccc1)c1ccccc1
Reactant: CC(=O)OO
Agent: [Na+]
Solvent: ClCCl
Product: O=C(OC(OC(=O)c1ccccc1)c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 158.4 %

Procedure:
32% peracetic acid (0.67 mL, 3.79 mmol) was added to a suspension of desyl benzoate (300 mg, 0.95 mmol) and Na2CO3 (402 mg, 3.79 mmol) in dichloromethane (5 mL) at 0° C. The reaction mixture was stirred overnight at room temperature, diluted with dichloromethane, washed with saturated NaHCO3 and brine and dried over Na2SO4. Concentration in vacuo provided 250 mg the title compound (79%). 1H NMR (CDCl3): δ 8.22 (1H, s); 7.73-7.71 (2H, m); 7.59-7.55 (2H, m); 7.48-7.42 (7H, m).