Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].C1COCC1.[OH:8][CH:9]([CH2:21][CH2:22][CH3:23])[CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([F:18])=[C:14]([F:19])[C:13]=1F.C1(C)C=CC=CC=1>CN(C=O)C>[F:18][C:15]1[C:14]([F:19])=[C:13]2[C:12]([CH2:11][CH2:10][CH:9]([CH2:21][CH2:22][CH3:23])[O:8]2)=[CH:17][CH:16]=1
Reactant: CCCC(O)CCc1ccc(F)c(F)c1F
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: CCCC1CCc2ccc(F)c(F)c2O1
Temperature: 50 °C
Reaction time: 3 h

Procedure:
Sodium hydride (60% in oil) was suspended in DMF under nitrogen replacement. Then, the THF solution containing 1-(3-hydroxy-1-hexyl)-2,3,4-trifluorobenzene was added dropwise for 30 minutes, and stirred for 3 hours at 50° C. After toluene was added and stirred for a while, an organic layer was separated and an aqueous layer was extracted with toluene. After the extract and the organic layer were mixed together, washed using water and a saturated saline solution in that order, and dried using anhydrous sodium sulfate, the solvent was evaporated under a reduced pressure. The residue was purified by column chromatography (silica gel, hexane) to obtain 7,8-difluoro-2-propylchroman.
Reaction SMILES: [CH2:1]([CH:3]1[CH2:8][CH2:7][CH2:6][CH:5]([CH3:9])[C:4]1=[N:10][CH:11]([CH3:15])[CH2:12][O:13][CH3:14])[CH3:2].C(N(CC)CC)C.[Cl:23][CH2:24][C:25](Cl)=[O:26]>C1C=CC=CC=1>[Cl:23][CH2:24][C:25]([N:10]([CH:11]([CH3:15])[CH2:12][O:13][CH3:14])[C:4]1[CH:5]([CH3:9])[CH2:6][CH2:7][CH2:8][C:3]=1[CH2:1][CH3:2])=[O:26]
Reactant: O=C(Cl)CCl
Reactant: CCC1CCCC(C)C1=NC(C)COC
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: CCC1=C(N(C(=O)CCl)C(C)COC)C(C)CCC1
Temperature: 25 °C
Yield: 63 %

Procedure:
174 g (0,83 mole) of 2-ethyl-6-methyl-N-(1-methyl-2-methoxy-ethyl)-cyclohexylideneamine and 101g (1 mole) of triethylamine were added dropwise one after the other with stirring and at a temperature of 5°C to a solution of 94 g (0,83 mole) of chloroacetyl chloride in 3000 ml of benzene. The reaction mixture was then refluxed for 5 hours, cooled to room temperature, washed with water, dried with sodium sulfate, filtered and concentrated under water-jet vacuum. Distillation of the residue under high vacuum gave 150,5 g of a 2-chloro-N-(1 -methyl-2-methoxy-ethyl)N-(2-ethyl-6-methyl-cyclohexenyl)acetamide as a mixture of its isomers b.p. 140°-148°/0.1 Torr.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]2=[N:12][N:13]=[C:14]([C:15]3[CH:19]=[CH:18][O:17][N:16]=3)[N:4]2[N:3]=1.[OH:20][CH2:21][C:22]1[N:26]([CH2:27][CH3:28])[N:25]=[N:24][CH:23]=1>>[CH2:27]([N:26]1[C:22]([CH2:21][O:20][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]3=[N:12][N:13]=[C:14]([C:15]4[CH:19]=[CH:18][O:17][N:16]=4)[N:4]3[N:3]=2)=[CH:23][N:24]=[N:25]1)[CH3:28]
Reactant: Clc1nn2c(-c3ccon3)nnc2c2ccccc12
Reactant: CCn1nncc1CO
Product: CCn1nncc1COc1nn2c(-c3ccon3)nnc2c2ccccc12

Procedure:
The title-compound was prepared from 6-chloro-3-(3-isoxazolyl) 1,2,4-triazolo[3,4-a]phthalazine (prepared as described in Example 34 step b) and 5-hydroxymethyl-1-ethyl-1,2,3-triazole (prepared as described in Example 97 part b), following the procedure given for Example 71 but performing the reaction at −456° C.; 1H NMR (360 MHz, CDCl3) δ 1.62 (3H, t, J=7.2 Hz, CH3), 4.58 (2H, q, J=7.3 Hz, CH2), 5.81 (2H, s, CH2), 7.25 (1H, d, J=1.8 Hz, Ar—H), 7.84 (1H, m, Ar—H), 7.99 (1H, m, Ar—H), 8.08 (1H, s, Ar—H), 8.14 (1H, d, J=7.8 Hz, Ar—H), 8.66 (1H, d, J=1.8 Hz, Ar—H), 8.72 (1H, d, J=7.8 Hz, Ar—H); MS (ES+) m/e 363 [MH]+; Anal. Found. d, 56.47; H 3.68; N, 30.82. C17H14N8O2 requires C, 56.35; H, 3.89; N, 30.92%.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Cl[CH2:8][C:9]1[CH:18]=[CH:17][C:16]([OH:19])=[C:15]2[C:10]=1[CH:11]=[CH:12][CH:13]=[N:14]2>C(Cl)(Cl)Cl>[O:4]1[CH2:5][CH2:6][N:1]([CH2:8][C:9]2[CH:18]=[CH:17][C:16]([OH:19])=[C:15]3[C:10]=2[CH:11]=[CH:12][CH:13]=[N:14]3)[CH2:2][CH2:3]1
Reactant: Oc1ccc(CCl)c2cccnc12
Reactant: C1COCCN1
Solvent: ClC(Cl)Cl
Product: Oc1ccc(CN2CCOCC2)c2cccnc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 58.9 %

Procedure:
Morpholine (1.9 ml; 21.8 mmol) was added to a solution of 5-chloromethyl-8-hydroxyquinoline (1.98 g; 8.34 mmol) in CHCl3 (50 ml) at 5° C. The reaction mixture was stirred overnight at room temperature. Then CHCl3 (100 ml) was added and the solution was washed with 5% NaHCO3 (2×50 ml), followed by brine (50 ml), and dried over Na2SO4. The solution was filtered and evaporated under vacuum to dryness. The residue was crystallized from hexane-CHCl3 and gave 1.2 g (59%) of the title product. M.p. 130° C. TLC (CHCl3; MeOH; NH3=8:2:0.5. Rf=0.69.
Reaction SMILES: C[O:2][C:3](=[O:36])[C@H:4]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:25]([C:27]2[CH:32]=[C:31]([C:33]#[N:34])[CH:30]=[CH:29][C:28]=2[Cl:35])=[O:26])=[CH:20][CH:19]=1)[NH:5][C:6]([C:8]1([CH2:13][CH2:14][O:15][CH3:16])[CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:7].[I-].[Li+].N1C=CC=CC=1>O>[Cl:35][C:28]1[CH:29]=[CH:30][C:31]([C:33]#[N:34])=[CH:32][C:27]=1[C:25]([NH:24][C:21]1[CH:22]=[CH:23][C:18]([CH2:17][C@@H:4]([C:3]([OH:36])=[O:2])[NH:5][C:6]([C:8]2([CH2:13][CH2:14][O:15][CH3:16])[CH2:12][CH2:11][CH2:10][CH2:9]2)=[O:7])=[CH:19][CH:20]=1)=[O:26]
Reactant: COCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3cc(C#N)ccc3Cl)cc2)C(=O)OC)CCCC1
Agent: [I-]
Agent: [Li+]
Solvent: O
Solvent: c1ccncc1
Product: COCCC1(C(=O)N[C@@H](Cc2ccc(NC(=O)c3cc(C#N)ccc3Cl)cc2)C(=O)O)CCCC1
Temperature: 25 °C
Yield: 40.2 %

Procedure:
To a mixture of 4-[(2-chloro-5-cyanophenylcarbonyl)amino]-N-[[1-(2-methoxy-ethyl)cyclopentyl]carbonyl]-L-phenylalanine methyl ester (0.1 mmol, 51 mg) and lithium iodide (1.0 mmol, 133 mg) was added pyridine (2 mL) at room temperature. The solution was refluxed for 15 h at which time TLC analysis of the mixutre indicated the absence of starting material. Then, the mixture was cooled to room temperature and diluted with water (15 mL) and the bulk of the pyridine was removed under reduced pressure. Then it was extracted with ether (2×15 mL) to remove any neutral impurities. The aqueous layer was acidified with 1N HCl and the precipitated white solid was collected by filtration and washed with 20 mL of water and 20 mL of hexane. After air-drying, the crude product was crystallized from acetonitrile to afford 20 mg (40%) of a white solid: mp 169-172° C. HR MS (C26H26ClN3O5): Obs mass, 498.1802. Calcd mass, 498.1795, M+H).
Reaction SMILES: [C:1]([OH:10])(=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].S(Cl)([Cl:13])=O>>[C:1]([Cl:13])(=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CCCCCCCC(=O)O
Reactant: O=S(Cl)Cl
Product: CCCCCCCC(=O)Cl

Procedure:
First, the n-octanoic acid is acylated by using thionyl dichloride to obtain n-octanoyl chloride, and the reaction equation is:
Reaction SMILES: C(N(CC)CC)C.[CH3:8][O:9][CH2:10]Cl.O1CCCC1.[F:17][C:18]1[CH:26]=[CH:25][C:21]([C:22]([OH:24])=O)=[CH:20][C:19]=1[OH:27]>C(OCC)(=O)C>[F:17][C:18]1[CH:26]=[CH:25][C:21]([CH2:22][OH:24])=[CH:20][C:19]=1[O:27][CH2:8][O:9][CH3:10]
Reactant: O=C(O)c1ccc(F)c(O)c1
Reactant: COCCl
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COCOc1cc(CO)ccc1F
Temperature: 0 °C
Reaction time: 2 h
Yield: 94 %

Procedure:
Triethylamine (1.07 mL) and methoxymethyl chloride (2.24 mL) were added to tetrahydrofuran (10 mL) solution of 4-fluoro-3-hydroxybenzoic acid (1.0 g), and stirred at 0° C. for 2 hours. Ethyl acetate was added to the reaction liquid which then was washed with water and saturated brine, dried over anhydrous magnesium sulfate, the solvent therein was concentrated under reduced pressure and the residue was dissolved in tetrahydrofuran (20 mL). Lithiumaluminium hydride (360 mg) was added, stirred at 0° C. for an hour, ethyl acetate was added and the insoluble matter was removed, followed by washing with saturated brine and drying over anhydrous magnesium sulfate. Concentrating the solvent under reduced pressure, the title compound (1.14 g, 94%) was obtained.
Reaction SMILES: [C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5]CC)=O.[Li].[N:13]1[CH:18]=[CH:17][N:16]=[CH:15][C:14]=1C(Cl)=O.Cl>C1COCC1>[O:5]=[C:3]([C:14]1[CH:15]=[N:16][CH:17]=[CH:18][N:13]=1)[CH2:2][C:1]([O:9][CH2:10][CH3:11])=[O:8]
Reactant: O=C(Cl)c1cnccn1
Reactant: CCOC(=O)CC(=O)OCC
Agent: Cl
Agent: [Li]
Solvent: C1CCOC1
Product: CCOC(=O)CC(=O)c1cnccn1
Temperature: -78 °C
Reaction time: 0.17 h

Procedure:
To a stirred solution of diethyl malonate (1.25 ml, 1.32 g) in THF (20 ml) under an atmosphere of nitrogen at −60° C. was added nbutyl lithium (2.5 M, 9 ml) dropwise over 15 min, keeping the temperature constant. The reaction became a cloudy white colour from the formation of the di-lithium salt then became yellowish. After 10 min, the reaction was cooled to −78° C., when a solution of pyrazine-2-carbonyl chloride (0.5 g, dark purple solution in THF (10 ml)) was added dropwise over 15 min. The reaction then warmed to −45° C. and stirred for 1 h. The reaction was then poured into 1 M HCl solution (35 ml) with stirring. This was transferred to a separating funnel, and extracted with CH2Cl2 (2×150 ml). The combined organic layers were then washed with sat. NaCO3 soln (1×30 ml) and then dried over MgSO4, filtered and concentrated in vacuo to give the product as a brown oil. Yield 0.65 g, 45%.
Reaction SMILES: [CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][CH:2]2[C:8]1[S:12][N:11]=[C:10](SC)[N:9]=1.Cl[C:16]1C=C(C=CC=1)C(OO)=O.[S:26]([O-:29])(O)=[O:27].[Na+]>C(Cl)(Cl)Cl>[CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][CH:2]2[C:8]1[S:12][N:11]=[C:10]([S:26]([CH3:16])(=[O:29])=[O:27])[N:9]=1
Reactant: CSc1nsc(C2CC3CCC2C3)n1
Reactant: O=S([O-])O
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: CS(=O)(=O)c1nsc(C2CC3CCC2C3)n1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
1.0 g of 5-(2-norbornyl)-3-methylthio-1,2,4-thiadiazole was dissolved in 9 ml of chloroform, 3.67 g of 3-chloroperoxybenzoic acid (content>65%) was added thereto, and the reaction mixture was stirred for 30 minutes under ice-cooling and for 1 day at room temperature. Then, the reaction mixture was added to saturated sodium hydrogensulfite aqueous solution, and separated. The organic layer was washed with sodium hydrogencarbonate aqueous solution, dried over anhydrous sodium sulfate, concentrated to give 833 mg of 5-(2-norbornyl)-3-methylsulfonyl-1,2,4-thiadiazole.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([OH:12])=O.C(Cl)(=O)C(Cl)=O.[NH2:19][CH:20]([CH3:36])[C:21]([N:23]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:22]>>[C:24]1([N:23]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:21]([CH:20]([NH:19][C:10]([C:2]2[NH:1][C:9]3[C:4]([CH:3]=2)=[CH:5][CH:6]=[CH:7][CH:8]=3)=[O:12])[CH3:36])=[O:22])[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: O=C(O)c1cc2ccccc2[nH]1
Reactant: CC(N)C(=O)N(c1ccccc1)c1ccccc1
Agent: O=C(Cl)C(=O)Cl
Product: CC(NC(=O)c1cc2ccccc2[nH]1)C(=O)N(c1ccccc1)c1ccccc1
Yield: 83.6 %

Procedure:
Working in a manner similar to that described in Example 9, but starting with 2-indolcarboxylic acid (1.3 g), oxalyl dichloride (1 g) and (RS)-2-amino-N,N-diphenylpropionamide (1.2 g), and after recrystallization in acetonitrile, (RS)-N-(1-diphenylcarbamoylethyl)-2-indolcarboxamide (1.6 g), m.p. 242° C., is obtained.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8]([CH2:10][N:11]3[C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=4[S:14][CH:13]([CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:12]3=O)=[N:7][C:6]=2[CH:28]=1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:30]>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8]([CH2:10][N:11]3[C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=4[S:14][CH:13]([CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:12]3=[S:30])=[N:7][C:6]=2[CH:28]=1
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Reactant: CCOC(=O)CC1Sc2ccccc2N(Cc2nc3cc(F)ccc3s2)C1=O
Solvent: Cc1ccccc1
Product: CCOC(=O)CC1Sc2ccccc2N(Cc2nc3cc(F)ccc3s2)C1=S
Yield: 71.5 %

Procedure:
To 10 ml of toluene were added 720 mg of the compound of Example 1 and 770 mg of phosphorus pentasulfide. The mixture was heated to reflux for 4 hours. After the mixture has been cooled, the insoluble substance was filtered off and the solvent was distilled off. The residue was purified by silica gel chromatography to give 535 mg of the title compound. The structural formula and physical data of this compound are shown in Table 23.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([N+:23]([O-])=O)[C:5]([OH:22])=[C:6]([CH:21]=1)[CH:7]=[C:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1.C(=O)([O-])O.[Na+].Cl[CH2:32][C:33](Cl)=[O:34]>CO.[Pd].CC(=O)CC>[O:34]=[C:33]1[NH:23][C:4]2[CH:3]=[CH:2][CH:21]=[C:6]([CH2:7][CH:8]3[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]3)[C:5]=2[O:22][CH2:32]1
Reactant: CC(C)(C)OC(=O)N1CCC(=Cc2cc(Br)cc([N+](=O)[O-])c2O)CC1
Reactant: O=C(Cl)CCl
Agent: [Pd]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: CCC(C)=O
Product: CC(C)(C)OC(=O)N1CCC(Cc2cccc3c2OCC(=O)N3)CC1
Temperature: 0 °C
Reaction time: 2 h
Yield: 88.4 %

Procedure:
A solution of tert-butyl 4-(5-bromo-2-hydroxy-3-nitrobenzylidene)piperidine-1-carboxylate (2.1 g, 4.9 mmol) in methanol (150 mL) was stirred under atmospheric hydrogen in the presence of 10% palladium on charcoal (0.5 g) for 4 h. The catalyst was removed by filtration and the filtrate was evaporated in vacuo to give a crude oil (1.8 g) which was taken up in 2-butanone (30 mL) and aqueous sodium hydrogen carbonate (1.3 g in water 20 mL). Chloroacetyl chloride (0.78 g) was added dropwise at 0° C. The mixture was stirred at 0° C. for further 2 h and then at 80° C. for 4 h. It was partitioned between water (50 mL) and ethyl acetate (100 mL). The organic layer was evaporated in vacuo. Silica gel chromatography of the resulting residue eluting with ethyl acetate in petroleum ether (20–30%) gave the title compound (1.5 g) as an oil.
Reaction SMILES: [I:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.[C:9]1(=O)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.C[Si]([C:20]#[N:21])(C)C>C(O)(=O)C>[I:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:9]2([C:20]#[N:21])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[CH:4][CH:3]=1
Reactant: C[Si](C)(C)C#N
Reactant: Nc1ccc(I)cc1
Reactant: O=C1CCCCC1
Solvent: CC(=O)O
Product: N#CC1(Nc2ccc(I)cc2)CCCCC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
3 g (13.7 mmol, 1 eq.) of 4-iodoaniline are added to a solution of 1.4 ml (13.5 mmol, 1 eq.) of cyclohexanone in 20 ml of acetic acid at 0° C. The solution is stirred for a moment, and 1.8 ml (13.5 mmol, 1 eq.) of trimethylsilyl cyanide are added. The reaction medium is stirred overnight at room temperature. It is then poured gently into ice-cold ammonium hydroxide solution and extracted with dichloromethane. The organic phases are combined and washed with water. They are dried over sodium sulfate. The solvents are evaporated off and the residue is then chromatographed on silica gel. The product 1-(4-iodophenylamino)cyclohexanecarbonitrile is obtained in the form of a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[C:3]=1[C:4]([N:6]=[C:7]=[O:8])=[O:5].[CH3:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([NH:22][NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[CH:18][C:17]=1[C:31]([O:33][CH3:34])=[O:32]>C(Cl)Cl>[Cl:1][C:2]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[C:3]=1[C:4]([NH:6][C:7]([N:22]([C:19]1[CH:20]=[CH:21][C:16]([O:15][CH3:14])=[C:17]([C:31]([O:33][CH3:34])=[O:32])[CH:18]=1)[NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[O:8])=[O:5]
Reactant: COC(=O)c1cc(NNC(=O)OC(C)(C)C)ccc1OC
Reactant: O=C=NC(=O)c1c(F)cccc1Cl
Solvent: ClCCl
Product: COC(=O)c1cc(N(NC(=O)OC(C)(C)C)C(=O)NC(=O)c2c(F)cccc2Cl)ccc1OC
Yield: 89.6 %

Procedure:
The title compound was prepared according to the procedure described in step-1 of Intermediate-9 by using 2-chloro-6-fluorobenzoyl isocyanate (Intermediate-8, 2.0 g, 6.75 mmol), tert-butyl 2-[4-methoxy-3-(methoxycarbonyl)phenyl]hydrazinecarboxylate (Intermediate-10, 1.61 g, 8.18 mmol) and DCM (30 mL) to afford 3.0 g of desired product. 1H NMR (300 MHz, DMSO d6): δ 1.40 (s, 9H), 3.81 (s, 6H), 7.13-7.83 (m, 6H), 9.6 (br s, 1H), 11.13 (br s, 1H); MS (m/z): 494.05 (M−H)−.
Reaction SMILES: N1CCCCC1.C1C2C(COC(=O)[NH:23][CH:24]([CH2:48][C:49]3[CH:54]=[CH:53][C:52]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[CH:51][CH:50]=3)[C:25](=[O:47])[N:26]3[CH:35]([C:36]4[NH:37][CH:38]=[C:39]([C:41]5[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=5)[N:40]=4)[CH2:34][C:33]4[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=4)[CH2:27]3)C3C(=CC=CC=3)C=2C=CC=1>CO>[NH2:23][CH:24]([CH2:48][C:49]1[CH:54]=[CH:53][C:52]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[CH:51][CH:50]=1)[C:25]([N:26]1[CH:35]([C:36]2[NH:37][CH:38]=[C:39]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[N:40]=2)[CH2:34][C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH2:27]1)=[O:47]
Reactant: CC(C)(C)Oc1ccc(CC(NC(=O)OCC2c3ccccc3-c3ccccc32)C(=O)N2Cc3ccccc3CC2c2nc(-c3ccccc3)c[nH]2)cc1
Solvent: CO
Solvent: C1CCNCC1
Product: CC(C)(C)Oc1ccc(CC(N)C(=O)N2Cc3ccccc3CC2c2nc(-c3ccccc3)c[nH]2)cc1

Procedure:
Piperidine in methanol (20%; 2 mL) was added to {1-(4-tert-butoxy-benzyl)-2-oxo-2-[3-(4-phenyl-1H-imidazol-2-yl)-3,4-dihydro-1H-isoquinolin-2-yl]-ethyl}-carbamic acid 9H-fluoren-9-ylmethyl ester (0.20 g, 0.28 mmol) at room temperature. After 30 minutes the reaction was concentrated under reduced pressure, and the residual 200 mg of desired product 2-amino-3-(4-tert-butoxy-phenyl)-1-[3-(4-phenyl-1H-imidazol-2-yl)-3,4-dihydro-1H-isoquinolin-2-yl]-propan-1-one was used as is without further purification (LC/MS; Measured, MW (MH+):495).
Reaction SMILES: B(F)(F)F.[C]=O.C=C.[C:9]([O:13][CH3:14])(=[O:12])[CH2:10][CH3:11]>>[C:9]([O:13][CH3:14])(=[O:12])[CH:10]=[CH2:11].[C:9]([OH:13])(=[O:12])[CH:10]=[CH2:11]
Reactant: CCC(=O)OC
Agent: C=C
Agent: FB(F)F
Agent: [C]=O
Product: C=CC(=O)O
Product: C=CC(=O)OC
Temperature: 20 °C

Procedure:
In this example, 90 g. of a BF3.CH3OH complex is added to a 600 ml. autoclave and maintained at 20° C. A 9:1 carbon monoxide/ethylene gas mixture is added at 68 atms. After addition of this mixture, the autoclave is heated to 50° C. and maintained at this temperature for three hours. The autoclave is cooled and depressurized. Analysis by gas-liquid chromatography indicates that the autoclave contents consist of 1 to 2% by weight methyl propionate plus 2 to 3% by weight of heavier materials. The selectivity to methyl propionate is about 25%. Under the conditions of the oxidative dehydrogenation described in Example 1, methyl propionate gives a combined selectivity of 75% to methyl acrylate and acrylic acid.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([N:8]2[C@@H:12]([CH:13]([CH3:15])[CH3:14])[CH2:11][O:10][C:9]2=[O:16])[CH:5]=[CH:4][N:3]=1.[Cl:17][C:18]1[CH:19]=[C:20]([CH:25]([NH2:27])[CH3:26])[CH:21]=[CH:22][C:23]=1[Cl:24]>CS(C)=O.CCOC(C)=O>[Cl:17][C:18]1[CH:19]=[C:20]([C@H:25]([NH:27][C:2]2[N:7]=[C:6]([N:8]3[C@@H:12]([CH:13]([CH3:15])[CH3:14])[CH2:11][O:10][C:9]3=[O:16])[CH:5]=[CH:4][N:3]=2)[CH3:26])[CH:21]=[CH:22][C:23]=1[Cl:24].[Cl:17][C:18]1[CH:19]=[C:20]([C@@H:25]([NH:27][C:2]2[N:7]=[C:6]([N:8]3[C@@H:12]([CH:13]([CH3:15])[CH3:14])[CH2:11][O:10][C:9]3=[O:16])[CH:5]=[CH:4][N:3]=2)[CH3:26])[CH:21]=[CH:22][C:23]=1[Cl:24]
Reactant: CC(C)[C@H]1COC(=O)N1c1ccnc(Cl)n1
Reactant: CC(N)c1ccc(Cl)c(Cl)c1
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CC(C)[C@H]1COC(=O)N1c1ccnc(N[C@@H](C)c2ccc(Cl)c(Cl)c2)n1
Product: CC(C)[C@H]1COC(=O)N1c1ccnc(N[C@H](C)c2ccc(Cl)c(Cl)c2)n1

Procedure:
A solution of (S)-3-(2-chloropyrimidin-4-yl)-4-isopropyloxazolidin-2-one (93 mg, 0.38 mmol) and 1-(3,4-dichlorophenyl)ethanamine (73.1 mg, 0.385 mmol, 1.0 equiv) in DMSO (1 mL) was heated at 110° C. for 1½ h. The reaction mixture was diluted with EtOAc (8 mL) and washed with water (30 mL). After separation, the aqueous phase was extracted with EtOAc (3×8 mL). Combined organics were dried over Na2SO4, filtered and concentrated. Silica gel column chromatography (EtOAc/Heptane 10 to 50%) provided (S)-3-(2-((R)-1-(3,4-dichlorophenyl)ethylamino)pyrimidin-4-yl)-4-isopropyloxazolidin-2-one and (S)-3-(2-((S)-1-(3,4-dichlorophenyl)ethylamino)pyrimidin-4-yl)-4-isopropyloxazolidin-2-one.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:9]([O:11][CH3:12])=[O:10])=[CH:4][CH:3]=1.[CH3:19][O:20][C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.C(OCC)(=O)C.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>[CH3:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([C:2]2[CH:7]=[CH:6][C:5]([CH:8]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:9]([O:11][CH3:12])=[O:10])=[CH:4][CH:3]=2)=[CH:23][CH:22]=1
Reactant: COC(=O)C(c1ccccc1)c1ccc(Br)cc1
Reactant: COc1ccc(B(O)O)cc1
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: CCOC(C)=O
Solvent: COCCOC
Solvent: O
Product: COC(=O)C(c1ccccc1)c1ccc(-c2ccc(OC)cc2)cc1
Temperature: 80 °C
Reaction time: 16 h
Yield: 30.6 %

Procedure:
To a degassed solution of bromide 54 (0.33 g, 1.081 mmol), 4-methoxyphenylboronic acid (0.181 g, 1.190 mmol), POT (0.023 g, 0.076 mmol) and potassium carbonate (0.747 g, 5.41 mmol) in DME (15 mL) and water (7.5 mL) was added Pd(PPh3)4 (0.087 g, 0.076 mmol). The reaction mixture was stirred at 80° C. for 16 h and diluted with ethyl acetate, washed with water, dried over Na2SO4, filtered and concentrated to afford compound 55 (0.11 g, 31% yield) as a white solid after purification by ISCO (2 to 40% EtOAc/hexane).
Reaction SMILES: [NH2:1][C:2]1[C:10]([CH3:11])=[CH:9][C:8]([F:12])=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[CH3:13][N:14]1[CH2:19][CH2:18][N:17]([C:20]2[CH:27]=[CH:26][C:23]([CH:24]=O)=[CH:22][CH:21]=2)[CH2:16][CH2:15]1.S(OS([O-])=O)([O-])=O.[Na+].[Na+]>CN1CCCC1=O>[F:12][C:8]1[CH:7]=[C:3]2[C:2](=[C:10]([CH3:11])[CH:9]=1)[N:1]=[C:24]([C:23]1[CH:22]=[CH:21][C:20]([N:17]3[CH2:16][CH2:15][N:14]([CH3:13])[CH2:19][CH2:18]3)=[CH:27][CH:26]=1)[NH:6][C:4]2=[O:5]
Reactant: CN1CCN(c2ccc(C=O)cc2)CC1
Reactant: Cc1cc(F)cc(C(N)=O)c1N
Agent: O=S([O-])OS(=O)[O-]
Agent: [Na+]
Solvent: CN1CCCC1=O
Product: Cc1cc(F)cc2c(=O)[nH]c(-c3ccc(N4CCN(C)CC4)cc3)nc12
Temperature: 0 °C
Reaction time: 16 h

Procedure:
A solution of 2-amino-5-fluoro-3-methyl-benzamide (84.1 mg, 0.50 mmol), 4-(4-methyl-piperazin-1-yl)-benzaldehyde (123 mg, 0.60 mmol) and sodium disulfite (97 mg, 0.51 mmol) in N-methyl-pyrrolidone (1 ml) is heated to 150° C. and stirred at this temperature for 16 hours. The reaction mixture is allowed to reach room temperature and poured into ice water. The resulting precipitate is collected by filtration, washed with water and dried. The residue is chromatographed on a silica gel column with methanol/dichloromethane as eluent to afford 6-fluoro-8-methyl-2-[4-(4-methyl-piperazin-1-yl)-phenyl]-3H-quinazolin-4-one as brown powder; HPLC/MS 1.47 min (A), [M+H] 353; 1H NMR (400 MHz, DMSO-d6) δ [ppm] 12.34 (s, 1H), 8.69-7.90 (m, 2H), 7.86-7.26 (m, 2H), 7.28-6.73 (m, 2H), 3.33-3.27 (m, 4H), 2.61 (s, 3H), 2.45 (t, J=5.1 Hz, 4H), 2.23 (s, 3H).