Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([OH:7])[CH2:2][O:3][CH2:4][CH2:5][OH:6].[CH:8](OCC)=[CH2:9]>>[CH:8]([O:7][CH2:1][CH2:2][O:3][CH2:4][CH2:5][OH:6])=[CH2:9]
Reactant: OCCOCCO
Reactant: C=COCC
Product: C=COCCOCCO
Reaction time: 10 h
Yield: 37.5 %

Procedure:
Diethylene glycol (85 g, 0.8 mol), ethyl vinyl ether (80 ml, 0.8 mol) and, as the catalyst, mercuric acetate Hg(CH3COO)2 are charged to a 3-neck flask of 250 ml, equipped with condenser and inlets for the reactants and an inert gas. The system is kept under refluxing conditions, at a temperature of 70°-80° C., for 10 hours. The product is recovered by extraction with methylene chloride and is separated from the corresponding divinyl ether by distillation. In that way, 40 g (0.3 mol) of diethylene glycol monovinyl ether is obtained, with a yield of 40%, and is added to a solution containing 40 ml of ethyl ether and 53 ml of pyridine. To the resulting mixture, kept at room temperature and under a flowing nitrogen stream, methacryloyl chloride (38.3 g, 0.37 mol) is added dropwise. The addition of the chloride causes the immediate precipitation of pyridinium hydrochloride. The reaction is discontinued when the disappearance of the monovinyl ether is observed. The product (A) is recovered from the reaction mixture via HPLC, using silica as the stationary phase and a mixture of 8:1 hexane:ethylacetate as the eluent. 42 g of 99%-pure product is obtained, which corresponds to a yield of 70% relatively to diethylene glycol monovinyl ether.
Reaction SMILES: [Cu][C:2]#[N:3].[C-]#N.[Na+].[NH2:7][C:8]1[C:13](Br)=[N:12][C:11]([Br:15])=[CH:10][N:9]=1>CN(C=O)C>[NH2:7][C:8]1[C:13]([C:2]#[N:3])=[N:12][C:11]([Br:15])=[CH:10][N:9]=1
Reactant: N#C[Cu]
Reactant: Nc1ncc(Br)nc1Br
Agent: [C-]#N
Agent: [Na+]
Solvent: CN(C)C=O
Product: N#Cc1nc(Br)cnc1N
Temperature: 125 °C
Yield: 67.2 %

Procedure:
A solution of copper(i) cyanide (1.20 g, 13.42 mmol) and sodium cyanide (0.658 g, 13.42 mmol) in DMF (10 mL) was heated to 125° C. 2-amino-3,5-dibromo pyrazine (2.61 g, 10.32 mmol) was added in portions. The reaction was stirred at 125° C., and after 5 h quenched in ice cold NaHCO3 solution. The black precipitate was filtrated off and the filtrate was extracted (3×) with EtOAc. The organic layer was washed with brine, dried and evaporated. Purification by chromatography (CH2Cl2) gave pure 3-amino-6-bromopyrazine-2-carbonitrile 14 (1.38 g, 67.2%). 1H-NMR (400 MHz, CDCl3) 5.29 (br s, 2H), 8.30 (s, 1H). (m/z)=199 and 201 (M+H)+.
Reaction SMILES: [N:1]1([CH2:6][C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:8])[CH:5]=[N:4][CH:3]=[N:2]1.C(OCC)C.[CH3:20][Si:21]([CH2:24][Mg]Cl)([CH3:23])[CH3:22].Cl>O1CCCC1>[C:9]1([C:7]([OH:8])([CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH2:6][N:1]2[CH:5]=[N:4][CH:3]=[N:2]2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: C[Si](C)(C)C[Mg]Cl
Reactant: O=C(Cn1cncn1)c1ccccc1
Agent: Cl
Solvent: C1CCOC1
Solvent: CCOCC
Product: C[Si](C)(C)CC(O)(Cn1cncn1)c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 15 %

Procedure:
0.505 g (2.7 mmole) of 2-(1H-1,2,4-triazol-1-yl)-acetophenone was added to 50 ml of diethyl ether. The solution was then stirred at room temperature under a stream of nitrogen, and 13.5 ml (13.5 mmole) of a 1 M tetrahydrofuran solution of trimethylsilylmethylmagnesium chloride were added dropwise at such a rate that the temperature of the reaction mixture did not rise higher than 25° C. After the addition was complete, the reaction mixture was stirred for 30 minutes at room temperature; it was then heated under reflux for 6 hours. At the end of this time, the reaction mixture was cooled, and it was then poured into 100 ml of ice-water. Its pH was adjusted to a value of 6 by the addition of 5% w/v aqueous hydrochloric acid, after which it was extracted three times, each time with 50 ml of ethyl acetate. The organic layers were collected, washed three times, each time with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, and then the solvent was removed by distillation under reduced pressure, to afford a crude oily product. 0.112 g (yield 15%) of the title compound, melting at 86°-87° C., was obtained from this crude oily product by purification through a silica gel chromatography column, eluted with mixtures of ethyl acetate and hexane ranging from 1:1 to 2:1 by volume.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[C:18]([N+:23]([O-:25])=[O:24])[CH:17]=1.C(O)C.[CH3:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[C:36]([N:38]=[C:39]=[S:40])=[O:37]>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:39]([NH:38][C:36](=[O:37])[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=2[CH3:29])=[S:40])=[C:18]([N+:23]([O-:25])=[O:24])[CH:17]=1
Reactant: COc1cc2nccc(Oc3ccc(N)c([N+](=O)[O-])c3)c2cc1OC
Reactant: Cc1ccccc1C(=O)N=C=S
Solvent: CCO
Solvent: Cc1ccccc1
Product: COc1cc2nccc(Oc3ccc(NC(=S)NC(=O)c4ccccc4C)c([N+](=O)[O-])c3)c2cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 80 %

Procedure:
4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-nitroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 2-methyl-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (66 mg, yield 80%).
Reaction SMILES: [C:1]([S:4][CH2:5][CH:6]([CH3:10])[C:7](Cl)=[O:8])(=[O:3])[CH3:2].[CH2:11]([CH:13]1[NH:17][CH:16]([C:18]([OH:20])=[O:19])[CH2:15][S:14]1)[CH3:12]>[OH-].[Na+]>[C:1]([S:4][CH2:5][CH:6]([CH3:10])[C:7]([N:17]1[CH:16]([C:18]([OH:20])=[O:19])[CH2:15][S:14][CH:13]1[CH2:11][CH3:12])=[O:8])(=[O:3])[CH3:2]
Reactant: CC(=O)SCC(C)C(=O)Cl
Reactant: CCC1NC(C(=O)O)CS1
Agent: [Na+]
Agent: [OH-]
Product: CCC1SCC(C(=O)O)N1C(=O)C(C)CSC(C)=O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
3-Acetylthio-2-methylpropanoic acid chloride (5.4 g. prepared from 3-acetylthio-2-methylpropanoic acid and thionyl chloride, b.p. 80°) and 2 N sodium hydroxide (15 ml.) are added to a solution of 2-ethyl-4-thiazolidinecarboxylic acid [Z. Naturforschg, 17b, 765 (1962)] (5.2 g.) in normal sodium hydroxide (30 ml.) chilled in an ice-water bath. After three hours stirring at room temperature, the mixture is extracted with ether, the aqueous phase is acidified and extracted with ethyl acetate. The organic phase is dried over magnesium sulfate and concentrated to dryness in vacuo to yield 3-(3-acetylthio-2-methylpropanoyl)-2-ethyl-4- thiazolidinecarboxylic acid.
Reaction SMILES: N[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][N:3]=1.S(=O)(=O)(O)[OH:10].[N+:14]([O-])([OH:16])=[O:15]>>[Cl:8][C:5]1[CH:6]=[C:7]([N+:14]([O-:16])=[O:15])[C:2](=[O:10])[NH:3][CH:4]=1
Reactant: Nc1ccc(Cl)cn1
Reactant: O=[N+]([O-])O
Reactant: O=S(=O)(O)O
Product: O=c1[nH]cc(Cl)cc1[N+](=O)[O-]
Temperature: 0 °C

Procedure:
2-Amino-5-chloropyridine (12.8 g., 0.1 mole) was added to 50 ml. of concentrated sulfuric acid. To this was slowly added with stirring 25 ml. of concentrated nitric acid. After the exothermic reaction subsided, the mixture was cooled and poured onto ice. The precipitate was collected and added to a mixture of 12 ml. of concentrated sulfuric acid and 150 ml. of water. To this solution cooled to 0° C., was added 7 g. of sodium nitrite portionwise and the resulting mixture was allowed to warm spontaneously to room temperature. After cooling the precipitate was collected and recrystallized from dimethyl formamideethanol to give 5-chloro-3-nitro-2-pyridone, m.p. 225-227.
Reaction SMILES: CN(C)C=O.C(=O)([O-])[O-].[K+].[K+].I[C:13]1[C:18]([O:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:32][CH3:33])=[C:27]([O:30][CH3:31])[CH:28]=3)[N:23]=[CH:22][CH:21]=2)=[CH:17][CH:16]=[C:15]([CH3:34])[N:14]=1.[N:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=1>O.C(O)C>[CH3:31][O:30][C:27]1[CH:28]=[C:29]2[C:24](=[CH:25][C:26]=1[O:32][CH3:33])[N:23]=[CH:22][CH:21]=[C:20]2[O:19][C:18]1[C:13]([C:38]2[CH:39]=[CH:40][N:35]=[CH:36][CH:37]=2)=[N:14][C:15]([CH3:34])=[CH:16][CH:17]=1
Reactant: COc1cc2nccc(Oc3ccc(C)nc3I)c2cc1OC
Reactant: OB(O)c1ccncc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCO
Product: COc1cc2nccc(Oc3ccc(C)nc3-c3ccncc3)c2cc1OC
Temperature: 70 °C
Reaction time: 3 h
Yield: 65.6 %

Procedure:
N,N-Dimethylformamide (1 ml), ethanol (0.5 ml), and a 2 M aqueous potassium carbonate solution (1 ml) were added to 4-(2-iodo-6-methyl-pyridin-3-yloxy)-6,7-dimethoxy-quinoline (compound 116) (50 mg), tetrakistriphenylphosphine palladium (14 mg) and 4-pyridylboronic acid (44 mg) under an argon atmosphere, and the mixture was stirred at 70° C. for 3 hr. The reaction solution was cooled to room temperature, water was then added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography using chloroform-methanol to give the title compound (29 mg, yield 66%).
Reaction SMILES: [CH3:1][N:2]1[C:10]2[CH2:9][CH2:8][C:7]3[CH:11]=[CH:12][CH:13]=[CH:14][C:6]=3[C:5]=2[CH2:4][CH2:3]1.[CH:15]([Mg]Cl)([CH3:17])[CH3:16].BrC(Cl)C.[Na+].[Na+].[Na+].[Na+].C(N(CC([O-])=O)CC([O-])=O)CN(CC([O-])=O)C[C:32]([O-])=[O:33]>O1CCCC1>[CH:15]1([CH2:1][N:2]2[C:10]3[CH2:9][CH2:8][C:7]4[CH:11]=[CH:12][C:13]([O:33][CH3:32])=[CH:14][C:6]=4[C:5]=3[CH2:4][CH2:3]2)[CH2:17][CH2:16]1
Reactant: CC(C)[Mg]Cl
Reactant: O=C([O-])CN(CCN(CC(=O)[O-])CC(=O)[O-])CC(=O)[O-]
Reactant: CN1CCC2=C1CCc1ccccc12
Agent: CC(Cl)Br
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1ccc2c(c1)C1=C(CC2)N(CC2CC2)CC1

Procedure:
This compound was prepared according to the procedure described by Evans, et al., J. Org. Chem. 35, 4122 (1970) for the synthesis of 3-methyl-1,2,4,5-tetrahydro-3H-benz[e]indole as follows. Into a dry, nitrogen filled, one liter 3-neck flask fitted with reflux condenser, serum cap, dropping funnel and magnetic stirrer, was added a solution of 38.55 g (167.9 mmol) XIIa in dry tetrahydrofuran (THF) (50 ml) which was placed under a slow stream of nitrogen. A 2.20 M solution of isopropyl magnesium chloride in THF (96.1 ml, 211.7 mmol) was added slowly via a syringe at such a rate as to maintain gentle reflux. After the addition (15 min), 30.72 g (214.2 mmol) of bromochloroethan was added to the warm reaction mixture at a rate sufficient to maintain gentle refluxing. After the addition of the alkylhalide, an additional 52.3 ml (115 mmol) of the Grignard reagent was added to the reaction again at a controlled rate. The reaction mixture was cooled in an ice-bath and 270 ml of 1 M aqueous solution of ethylenediaminetetraacetic acid tetrasodium salt was added slowly (with stirring) and then 600 ml of a 1:1 ether-benzene was added. The organic layer was separated and the aqueous phase was extracted with ether. The combined extracts were washed with water (2×100 ml) and dried (MgSO4). Removal of the solvent by evaporation gave 43.0 g (99%) of XIIIa as a pale yellow oxygen-sensitive oil; IR (neat), 1635 cm-1 (C=C--N).
Reaction SMILES: [NH:1]1[CH2:7][CH2:6][CH2:5][CH2:4][C:3]2[CH:8]=[CH:9][CH:10]=[CH:11][C:2]1=2.[CH3:12][N:13]1[CH2:18][CH2:17][C:16](=O)[CH2:15][CH2:14]1.C(O)(=O)C.[BH3-]C#N.[Na+]>CO>[CH3:12][N:13]1[CH2:18][CH2:17][CH:16]([N:1]2[CH2:7][CH2:6][CH2:5][CH2:4][C:3]3[CH:8]=[CH:9][CH:10]=[CH:11][C:2]2=3)[CH2:15][CH2:14]1
Reactant: c1ccc2c(c1)CCCCN2
Reactant: CN1CCC(=O)CC1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: CN1CCC(N2CCCCc3ccccc32)CC1
Reaction time: 15 h
Yield: 49.4 %

Procedure:
A solution of compound 2 (1.0 g, 6.79 mmol), N-methyl-4-piperidone (1.00 mL, 8.15 mmol) and acetic acid (0.96 mL, 16.98 mmol) in dry methanol (10 mL) was treated with NaCNBH3 (0.51 g, 8.15 mmol) at 0° C. The reaction mixture was brought to room temperature and stirred overnight (15 hours). The reaction was quenched with 2N NaOH (100 mL) and extracted with CH2Cl2 (2×25 mL). The combined organic fractions were washed with brine (30 mL), dried (Na2SO4) and concentrated. The crude product was purified by column chromatography (2.0 N NH3 in MeOH:CH2Cl2, 3:97) to give compound 3 (0.82 g, 49.4%) as a yellow oil. 1H-NMR (DMSO-d6) δ 1.55 (m, 4H), 1.74 (m, 4H), 1.96 (td, 2H, J=11.3, 2.6 Hz), 2.15 (s, 3H), 2.66 (m, 2H), 2.78 (m, 2H), 2.93 (m, 2H), 3.17 (m, 1H), 6.74 (t, 1H, J=7.3 Hz), 6.90 (d, 1H, J=8.2 Hz), 7.01 (m, 2H); EI-MS (m/z, %): 244 (M+, 24), 97 (100), 71 (37).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([S:9][C:10]2[N:14]([CH:15]([CH3:17])[CH3:16])[N:13]=[C:12]([CH3:18])[C:11]=2[CH:19](O)[C:20]2[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.C(N(S(F)(F)[F:33])CC)C>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([S:9][C:10]2[N:14]([CH:15]([CH3:17])[CH3:16])[N:13]=[C:12]([CH3:18])[C:11]=2[CH:19]([F:33])[C:20]2[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: CCN(CC)S(F)(F)F
Reactant: Cc1nn(C(C)C)c(Sc2cc(Cl)cc(Cl)c2)c1C(O)c1ccncc1
Solvent: ClCCl
Product: Cc1nn(C(C)C)c(Sc2cc(Cl)cc(Cl)c2)c1C(F)c1ccncc1
Temperature: -78 °C
Reaction time: 1 h

Procedure:
To a −78° C. solution of 200 mg of 4-[[5-(3,5-dichloro-phenylsulfanyl)-1-isopropyl-3 methyl-1H-pyrazol-4-yl]-hydroxy-methyl]-pyridine in 5 mL of dichloromethane was added 68 μL of diethylamino sulfur trifluoride. The reaction mixture was stirred for 1 hour at −78° C. then quenched with saturated aqueous sodium hydrogen carbonate. The aqueous phase was extracted three times with 10 mL of dichloromethane and combined extracts were washed with brine, dried, filtered and evaporated to give a blue gum which was purified by flash chromatography on silica gel using diethyl ether/hexane (1:2 then 1:1) for the elution to give 118 mg of 4-[[5-(3,5-Dichloro-phenylsulfanyl)-1-isopropyl-3-methyl-1H-pyrazol-4-yl]-fluoro-methyl]-pyridine as a colourless oil. Mass spectrum (ES) m/z 410 [M+H]+, 451 [M+H+MeCN]+.
Reaction SMILES: Cl.[F:2][C:3]1[C:16]([F:17])=[CH:15][C:6]([O:7][CH2:8][CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[C:5]([O:18][CH3:19])[CH:4]=1.Br[CH2:21][CH2:22][NH:23][C:24]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[F:2][C:3]1[C:16]([F:17])=[CH:15][C:6]([O:7][CH2:8][CH:9]2[CH2:14][CH2:13][N:12]([CH2:21][CH2:22][NH:23][C:24]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH2:11][CH2:10]2)=[C:5]([O:18][CH3:19])[CH:4]=1
Reactant: COc1cc(F)c(F)cc1OCC1CCNCC1
Reactant: BrCCNC(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1cc(F)c(F)cc1OCC1CCN(CCNC(c2ccccc2)(c2ccccc2)c2ccccc2)CC1
Temperature: 90 °C
Yield: 41.5 %

Procedure:
5.88 g (0.020 mol) of 4-[(4,5-difluoro-2-methoxyphenoxy)methyl]piperidine hydrochloride, 7.7 g (0.021 mol) of 2-bromo-N-(triphenylmethyl)ethylamine and 6.91 g (0.050 mol) of K2CO3 in 40 ml of DMF are reacted. The reaction mixture is heated to 90° C. for 8 hours. It is cooled to room temperature, poured into 500 ml of water and extracted 3 times with ethyl acetate. The organic phases are combined, washed with water, dried over MgSO4 and filtered, and the solvent is evaporated off under reduced pressure. The product is obtained in the form of an oil after chromatography. Yield: 41.5%.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([OH:12])=O.Cl.[C:14]1([C:20]2([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH:28]3[CH:24]([CH2:25][NH:26][CH2:27]3)[C:23](=[O:29])[CH2:22][CH2:21]2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(N(CC)CC)C>ClCCl>[C:30]1([C:20]2([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C@H:28]3[C@H:24]([CH2:25][N:26]([C:10](=[O:12])[CH2:9][C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])[CH2:27]3)[C:23](=[O:29])[CH2:22][CH2:21]2)[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1
Reactant: O=C1CCC(c2ccccc2)(c2ccccc2)C2CNCC12
Reactant: COc1ccccc1CC(=O)O
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccccc1CC(=O)N1C[C@@H]2C(=O)CCC(c3ccccc3)(c3ccccc3)[C@@H]2C1
Reaction time: 0.67 h
Yield: 64.3 %

Procedure:
N,N'-Carbonyldiimidazole (1 g) is added to a solution of 2-methoxyphenylacetic acid (1 g) in dry dichloromethane (30 cc), cooled to +5° C. The mixture is stirred for 40 minutes at +5° C. and a solution of (3aRS,7aRS)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (2 g) and triethylamine (1.7 cc) in dichloromethane (40 cc) is then added. The reaction mixture is stirred at 20° C. for 16 hours, then washed with water (2×50 cc), dried over magnesium sulphate and filtered and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a silica gel column (0.2-0.063 mm, diameter 1.8 cm, height 13 cm), eluting with ethyl acetate and collecting 25 cc fractions. Fractions 3 to 5 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from a mixture of acetonitrile (5 cc) and isopropyl ether (10 cc). The crystals are drained, washed with isopropyl ether (25 cc) and dried. (3aR,7aR)-(-)-7,7-diphenyl-2-[(2-methoxyphenyl)acetyl]-4-perhydroisoindolone (1.7 g) is obtained in the form of white crystals melting at 200° C.; [α]20D =-274° (c=0.49, acetic acid).
Reaction SMILES: C[O:2][C:3]([C:5]1[N:10]=[CH:9][CH:8]=[CH:7][N:6]=1)=O.O.[NH2:12][NH2:13]>CCO>[N:6]1[CH:7]=[CH:8][CH:9]=[N:10][C:5]=1[C:3]([NH:12][NH2:13])=[O:2]
Reactant: NN
Reactant: COC(=O)c1ncccn1
Solvent: O
Solvent: CCO
Product: NNC(=O)c1ncccn1
Reaction time: 0.08 h
Yield: 72.4 %

Procedure:
To a slurry of methylpyrimidine-2-carboxylate (1.0 g, 7.2 mmol) in EtOH (5.6 mL) was added hydrazine monohydrate (0.72 mL, 14 mmol). The reaction mixture became homogeneous and after 5 min a precipitate formed. Stirring was continued for 1 h. The mixture was filtered, and the collected solid was washed with additional EtOH to provide the desired product as a beige solid (720 mg, 72%). MS (ESI): mass calcd. C5H6N4O, 138.1; m/z found, 139.1 [M+H]+. 1H NMR (500 MHz, DMSO-d6): 10.06 (s, 1H), 8.92 (d, J=4.9 Hz, 2H), 7.64 (t, J=4.9 Hz, 1H), 4.64 (s, 2H).
Reaction SMILES: [Li][P:2]([C:7]([CH3:10])([CH3:9])[CH3:8])[C:3]([CH3:6])([CH3:5])[CH3:4].[Li][As](C(C)(C)C)C(C)(C)C.[Al:21](Cl)([C:26]([CH3:29])([CH3:28])[CH3:27])[C:22]([CH3:25])([CH3:24])[CH3:23]>>[Al:21]([P:2]([C:7]([CH3:10])([CH3:9])[CH3:8])[C:3]([CH3:6])([CH3:5])[CH3:4])([C:26]([CH3:29])([CH3:28])[CH3:27])[C:22]([CH3:25])([CH3:24])[CH3:23]
Reactant: [Li]P(C(C)(C)C)C(C)(C)C
Reactant: CC(C)(C)[Al](Cl)C(C)(C)C
Agent: [Li][As](C(C)(C)C)C(C)(C)C
Product: CC(C)(C)[Al](P(C(C)(C)C)C(C)(C)C)C(C)(C)C

Procedure:
The process of Example 1 was substantially followed except LiP(t-Bu)2 was substituted for LiAs(t-Bu)2 in the same molar proportions with respect to (t-Bu)2AlCl which was substituted for (t-Bu)2GaCl. The monomeric phosphinoalane, (t-Bu)2AlP(t-Bu)2, was produced. See NMR Table 1.
Reaction SMILES: ClC1C=C(C(OO)=[O:9])C=CC=1.[CH3:12][S:13][C:14]1[CH:15]=[N:16][CH:17]=[C:18]([C:20]#[C:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:19]=1>ClCCl>[CH3:12][S:13]([C:14]1[CH:15]=[N:16][CH:17]=[C:18]([C:20]#[C:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:19]=1)=[O:9]
Reactant: CSc1cncc(C#Cc2ccccc2)c1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CS(=O)c1cncc(C#Cc2ccccc2)c1
Reaction time: 2 h
Yield: 26.7 %

Procedure:
Add 3-chlorobenzenecarboperoxoic acid (27.61 mg, 0.16 mmol) to a cooled solution of 3-methylsulfanyl-5-phenylethynyl-pyridine, (prepared as described in EXAMPLE 128), (35.3 mg, 0.16 mmol) in dichloromethane (1 mL) at room temperature. Stir for 2 h and then quench with a 5% aqueous solution of sodium thiosulfite. Dilute with dichloromethane and separate the layers. Sequentially extract the organic layer with a 5% aqueous solution of sodium thiosulfite and an aqueous saturated solution of sodium chloride, dry (magnesium sulfate), filter and concentrate. Purify the residue by silica gel chromatography, eluting from 100:0 to 100:50 with hexanes:ethyl acetate, to give the title compound (10.3 mg, 27%).
Reaction SMILES: N12CCCN=C1CCCCC2.Cl.[NH2:13][CH2:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[C:17](=[O:33])[N:18]([CH:25]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32])[C:19]2=[O:24].[CH2:34]([N:38]=[C:39]=[O:40])[CH2:35][CH2:36][CH3:37]>CC#N>[O:32]=[C:26]1[CH:25]([N:18]2[C:17](=[O:33])[C:16]3[C:20](=[CH:21][CH:22]=[CH:23][C:15]=3[CH2:14][NH:13][C:39]([NH:38][CH2:34][CH2:35][CH2:36][CH3:37])=[O:40])[C:19]2=[O:24])[CH2:30][CH2:29][C:28](=[O:31])[NH:27]1
Reactant: NCc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O
Reactant: CCCCN=C=O
Agent: Cl
Solvent: CC#N
Solvent: C1CCC2=NCCCN2CC1
Product: CCCCNC(=O)NCc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O
Reaction time: 0.33 h
Yield: 61.6 %

Procedure:
1,8-Diazabicyclo[5,4,0]undec-7-ene (0.29 g, 1.90 mmol) was added to a stirred suspension of 4-(aminomethyl)-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione hydrochloride (0.6 g, 1.85 mmol) in CH3CN (50 mL). After stirring for 20 min, n-butyl isocyanate (0.27 g, 2.77 mmol) was added. The mixture was stirred at room temperature for 17 hours. The solvent was removed in vacuo and the residue was dissolved in CH2Cl2 (70 mL). The CH2Cl2 solution was washed with 1N HCl (30 mL), H2O (30 mL), brine (30 mL) and dried (MgSO4). The solvent was removed in vacuo and the residue was purified by chromatography (SiO2, CH2Cl2:EtOAc 1:1) to give N-{[2-(2,6-dioxo(3-piperidyl))1,3-dioxoisoindolin-4-yl]methyl}(butylamino)carboxamide (0.44 g, 61%) as a white solid: mp 172–174° C.; 1H NMR (DMSO-d6) δ 11.13 (s, 1H), 7.86–7.68 (m, 3H), 6.42 (t, J=5.9 Hz, 1H), 6.12 (t, J=5.4 Hz, 1H), 5.18–5.11 (dd, J=5.2 and 12.4 Hz, 1H), 4.63 (d, J=5.9 Hz, 1H), 3.03–2.83 (m, 3H), 2.64–2.51 (m, 2H), 2.08–2.04 (m, 1H), 1.37–1.22 (m, 4H), 0.86 (t, J=7.0 Hz, 3H); 13C NMR (DMSO-d6) δ 172.70, 169.77, 167.54, 167.00, 157.98, 141.14, 134.56, 133.33, 131.47, 126.94, 121.58, 48.80, 38.98, 38.70, 32.01, 30.90, 21.95, 19.46, 13.64; Anal. Calcd. For C19H22N4O5: C, 59.06; H, 5.74; N, 14.50. Found: C, 59.24; H, 5.53; N, 14.37.
Reaction SMILES: [F:1][C:2]1[C:7]([CH3:8])=[C:6]([F:9])[CH:5]=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[Br:16]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl>[Br:16][CH2:8][C:7]1[C:2]([F:1])=[C:3]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:4]=[CH:5][C:6]=1[F:9]
Reactant: Cc1c(F)ccc(-c2ccccc2)c1F
Reactant: O=C1CCC(=O)N1Br
Solvent: ClC(Cl)(Cl)Cl
Product: Fc1ccc(-c2ccccc2)c(F)c1CBr
Yield: 112.4 %

Procedure:
A stirred solution of 2,4-difluoro-3-methyl[1,1'-biphenyl] (2.2 g, 0.011 mole) and N-bromosuccinimide (1.9 g, 0.011 mole) in 100 ml of carbon tetrachloride was irradiated with a 250 watt infrared lamp for 4 hours. The reaction mixture was allowed to reflux from the heat of the lamp. The reaction mixture was then filtered, and the filter cake was washed with three portions of carbon tetrachloride. The washes and filtrate were combined and evaporated under reduced pressure to give 3-bromomethyl-2,4-difluoro[1,1'-biphenyl] (3.5 g) as an oil whose nmr spectrum was consistent with that expected for the named compound.