Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[CH:13]=[CH:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[N:9]=[CH:8][CH:7]=[C:6]2[O:20][C:21]1[C:22]([CH3:31])=[N:23][C:24]2[C:29]([CH:30]=1)=[CH:28][CH:27]=[CH:26][CH:25]=2>C(N(CC)CC)C.CN(C)C=O.[OH-].[Pd+2].[OH-]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[CH2:13][CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[N:9]=[CH:8][CH:7]=[C:6]2[O:20][C:21]1[C:22]([CH3:31])=[N:23][C:24]2[C:29]([CH:30]=1)=[CH:28][CH:27]=[CH:26][CH:25]=2
Reactant: CCOC(=O)C=Cc1cc2nccc(Oc3cc4ccccc4nc3C)c2cc1OC
Agent: [Pd+2]
Agent: [OH-]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCOC(=O)CCc1cc2nccc(Oc3cc4ccccc4nc3C)c2cc1OC
Temperature: 25 °C
Reaction time: 8 h
Yield: 25.7 %

Procedure:
Ethyl 3-[6-methoxy-4-(2-methyl-quinolin-3-yloxy)-quinolin-7-yl]-acrylate (compound 413) (310 mg) was dissolved in triethylamine/N,N-dimethylformamide (2.5 ml/13 ml) to prepare a solution. 20% palladium hydroxide (1.27 g) was added to the solution, and the mixture was stirred under a hydrogen gas atmosphere at room temperature overnight. The reaction solution was filtered, and the solvent was then removed by distillation under the reduced pressure. Water was added to the residue, 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 acetone-chloroform to give ethyl 3-[6-methoxy-4-(2-methyl-quinolin-3-yloxy)-quinolin-7-yl]-propionate (80 mg, yield 26%).
Reaction SMILES: Br[C:2]1[CH:35]=[CH:34][C:5]([CH2:6][C:7]2[N:8]([C:20]3[CH:25]=[CH:24][C:23]([N:26]4[S:30](=[O:32])(=[O:31])[NH:29][C:28](=[O:33])[CH2:27]4)=[CH:22][CH:21]=3)[CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=3[Cl:19])[N:11]=2)=[CH:4][CH:3]=1.[CH3:36][O:37][C:38]([C:40]1[CH:41]=[C:42](B(O)O)[CH:43]=[CH:44][CH:45]=1)=[O:39]>>[CH3:36][O:37][C:38]([C:40]1[CH:45]=[C:44]([C:2]2[CH:35]=[CH:34][C:5]([CH2:6][C:7]3[N:8]([C:20]4[CH:25]=[CH:24][C:23]([N:26]5[CH2:27][C:28](=[O:33])[NH:29][S:30]5(=[O:32])=[O:31])=[CH:22][CH:21]=4)[CH:9]=[C:10]([C:12]4[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=4[Cl:19])[N:11]=3)=[CH:4][CH:3]=2)[CH:43]=[CH:42][CH:41]=1)=[O:39]
Reactant: COC(=O)c1cccc(B(O)O)c1
Reactant: O=C1CN(c2ccc(-n3cc(-c4ccc(Cl)cc4Cl)nc3Cc3ccc(Br)cc3)cc2)S(=O)(=O)N1
Product: COC(=O)c1cccc(-c2ccc(Cc3nc(-c4ccc(Cl)cc4Cl)cn3-c3ccc(N4CC(=O)NS4(=O)=O)cc3)cc2)c1

Procedure:
5-{-4-[2-(4-Bromo-benzyl)-4-(2,4-dichloro-phenyl)-imidazol-1-yl]-phenyl}-1,2,5-thiadiazolidine-3-one-1,1-dioxide (119 mg, 0.2 mmol) was treated as described in general procedure G using 3-methoxycarbonylphenylboronic acid (108 mg, 0.6 mmol) to give 4′-{4-(2,4-dichloro-phenyl)-1-[4-(1,1,4-trioxo-[1,2,5]thiadiazolidin-2-yl)-phenyl]-1H-imidazol-2-ylmethyl}-biphenyl-3-carboxylic acid methyl ester.
Reaction SMILES: C([O:8][CH2:9][CH:10]([O:20][CH2:21][N:22]1[CH:29]=[C:28]([I:30])[C:26](=[O:27])[NH:25][C:23]1=[O:24])[CH2:11][O:12]CC1C=CC=CC=1)C1C=CC=CC=1.B(Cl)(Cl)Cl.CO.[NH4+].[OH-]>C(Cl)Cl>[OH:12][CH2:11][CH:10]([O:20][CH2:21][N:22]1[CH:29]=[C:28]([I:30])[C:26](=[O:27])[NH:25][C:23]1=[O:24])[CH2:9][OH:8]
Reactant: O=c1[nH]c(=O)n(COC(COCc2ccccc2)COCc2ccccc2)cc1I
Agent: ClB(Cl)Cl
Agent: [NH4+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CO
Product: O=c1[nH]c(=O)n(COC(CO)CO)cc1I
Temperature: -78 °C
Reaction time: 2 h
Yield: 65 %

Procedure:
To a solution of 45 (1.90 g, 3.64 mmol) in anhydrous CH2Cl2 (60 mL) at −78° C. was added BCl3 (1 M solution in CH2Cl2, 30 mL, 30 mmol) dropwise. The mixture was stirred at −78° C. under nitrogen for 2 h, then at −60° C. for another 4 h. MeOH (10 mL) was added to quench the reaction, followed by 14% NH4OH solution to adjust the mixture to pH 7. After being stirred at room temperature for 1 h, the mixture was concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with CH2Cl2/MeOH (9:1 to 4:1) to give the title compound 46 as a pale yellow solid (810 mg, 65%). 1H NMR (DMSO-d6) δ 11.6 (s, 1H, NH), 8.19 (s, 1H, H-6), 7.20, 6.60 (2br, 2H, 20H), 5.15 (s, 2H, CH2N), 4.60 (m, 2H, CH2O), 3.53 (m, 1H, CHO), 3.41 (m, 2H, 2 CH2O).
Reaction SMILES: B.O1CCCC1.[Br:7][C:8]1[CH:13]=[CH:12][C:11]([C@H:14]2[CH2:19][N:18]([C@@H:20]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH3:21])[C:17](=O)[CH2:16][O:15]2)=[CH:10][CH:9]=1.CO>O1CCCC1>[Br:7][C:8]1[CH:9]=[CH:10][C:11]([C@@H:14]2[O:15][CH2:16][CH2:17][N:18]([C@@H:20]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH3:21])[CH2:19]2)=[CH:12][CH:13]=1
Reactant: C[C@H](c1ccccc1)N1C[C@H](c2ccc(Br)cc2)OCC1=O
Agent: B
Solvent: CO
Solvent: C1CCOC1
Product: C[C@H](c1ccccc1)N1CCO[C@@H](c2ccc(Br)cc2)C1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 96.3 %

Procedure:
A borane-tetrahydrofuran complex (1.0M solution in tetrahydrofuran, 510 ml, 510 mm) was added to the ice-cooled solution of (6S)-6-(4-bromophenyl)-4-((1R)-1-phenyethyl)-morpholin-3-one (70.2 g) in tetrahydrofuran (500 ml) over 45 minutes and the solution was stirred at the same temperature for one hour and room temperature for 30 minutes. After careful addition of methanol (60 ml) to the ice-cooled solution, the solvent was removed under reduced pressure and the residue in methanol (750 ml) and 1M aqueous sodium hydroxide (280 ml) was stirred at 80° C. for one hour with addition of 1M aqueous sodium hydroxide (70 ml) in every 15 minutes. The solvent was removed under reduced pressure and the residue was partitioned between water and ethyl acetate. The organic layer was washed with water and brine and dried over anhydrous magnesium sulfate. Removal of the solvent yielded (2S)-2-(4-bromophenyl)-4-((1R)-1-phenylethyl)morpholine (65.0 g, 96.3% yield, 2 steps) as white crystals.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C@@H:12]([CH:13]=O)[CH2:11][O:10][C:9]1([CH3:16])[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:36](Br)(Br)([Br:38])[Br:37]>ClCCl>[C:1]([O:5][C:6]([N:8]1[C@@H:12]([CH:13]=[C:36]([Br:38])[Br:37])[CH2:11][O:10][C:9]1([CH3:16])[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1[C@@H](C=O)COC1(C)C
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1[C@@H](C=C(Br)Br)COC1(C)C
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 92 %

Procedure:
To a stirred, cooled (0° C.) solution of (R)-4-formyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (4.30 g; CAS 95715-87-0 and triphenylphosphine (9.15 g) in dichloromethane (100 ml) was added portionwise carbon tetrabromide (6.94 g). The mixture was stirred at 0° C. for 20 min and then at r.t. for 2 h. The mixture was concentrated in vacuo to ca 20 ml, then diluted with hexane (100 ml) and concentrated in vacuo to half-volume. The residue was stirred at 0° C. for 15 min, then the mixture was filtered and the filtrate was concentrated in vacuo to afford (S)-4-(2,2-dibromo-vinyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (6.18 g, 92%) as a colourless oil. MS (EI): 330.9 ([{81Br}M—C4H8]+), 328.9 ([{81 Br79 Br}M—C4H8]+), 326.9 ([{79 Br}M—C4H8]+).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([Mg]Br)[CH:5]=[CH:6][CH:7]=1.[N:10]12[CH2:17][CH2:16][C:13]([C:18]([O:20]CC)=O)([CH2:14][CH2:15]1)[CH2:12][CH2:11]2>C1COCC1>[N:10]12[CH2:11][CH2:12][C:13]([C:18]([C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([F:1])[CH:7]=3)([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)[OH:20])([CH2:14][CH2:15]1)[CH2:16][CH2:17]2
Reactant: Fc1cccc([Mg]Br)c1
Reactant: CCOC(=O)C12CCN(CC1)CC2
Solvent: C1CCOC1
Product: OC(c1cccc(F)c1)(c1cccc(F)c1)C12CCN(CC1)CC2
Temperature: 25 °C
Yield: 76.7 %

Procedure:
A solution of 3-fluorophenylmagnesiumbromide (1.0 M in THF, 3.3 mL, 3.3 mmol) was chilled down to 0° C. under Ar. Ethyl 1-azabicyclo[2.2.2]octane-4-carboxylate (0.1756 g, 0.958 mmol) in THF (4 mL) was slowly added to the reaction mixture at 0° C. over 20 min. The reaction was allowed to warm up to room temperature and then heated at 60° C. for 16 h. The reaction was chilled in an ice bath, quenched with saturated NH4Cl, and concentrated under vacuum. The resulting residue was treated with H2O and extracted with EtOAc. The combined organic layers were dried with MgSO4, filtered, and concentrated under vacuum to yield the desired product (0.242 g, 76.7%). EI-MS m/z 330(M+H+) Rt (1.45 min).
Reaction SMILES: N1CCCC1.[CH3:6][O:7][C:8]1[CH:29]=[CH:28][C:11]([C:12]([NH:14][C:15](=[O:27])[NH:16][C:17]2[CH:25]=[CH:24][CH:23]=[C:22]3[C:18]=2[CH2:19][C:20](=[O:26])[NH:21]3)=[O:13])=[CH:10][CH:9]=1.[NH:30]1[CH:34]=[CH:33][CH:32]=[C:31]1[CH:35]=O>C(O)C>[NH:30]1[CH:34]=[CH:33][CH:32]=[C:31]1/[CH:35]=[C:19]1\[C:20](=[O:26])[NH:21][C:22]2[C:18]\1=[C:17]([NH:16][C:15]([NH:14][C:12](=[O:13])[C:11]1[CH:10]=[CH:9][C:8]([O:7][CH3:6])=[CH:29][CH:28]=1)=[O:27])[CH:25]=[CH:24][CH:23]=2
Reactant: O=Cc1ccc[nH]1
Reactant: COc1ccc(C(=O)NC(=O)Nc2cccc3c2CC(=O)N3)cc1
Solvent: CCO
Solvent: C1CCNC1
Product: COc1ccc(C(=O)NC(=O)Nc2cccc3c2/C(=C/c2ccc[nH]2)C(=O)N3)cc1
Temperature: 25 °C

Procedure:
A catalytic amount of pyrrolidine (0.001 mmol) was added to a solution of 4-methoxy-N-(2-oxoindolin-4-ylcarbamoyl)benzamide (1 mmol) and pyrrole-2-carbaldehyde (1.2 mmol) in ethanol (5 mL). The reaction was carried out using microwave (CEM, Discover) at 100° C. (200 W. Standard mode) for 15 mins. Crude product was precipitated after cooling to RT, which was collected by filtration, washed with ethanol and air dried. YD: 65.57%; mp: Charred at 290-295° C. 1H NMR (DMSO-d6) 200 MHz, δ: 3.859 (s, 3H), 6.342-6.363 (m, 1H), 6.722-6.731 (m, 1H), 6.748 (d, J=7.6 Hz, 1H), 7.101 (d, J=9.2 Hz, 2H), 7.160 (t, J=8.0 Hz, 1H), 7.354 (br, 1H), 7.436 (d, J=8.0 Hz, 1H), 8.043 (s, 1H), 8.126 (d, J=8.8 Hz, 2H), 10.894 (s, 1H), 11.028 (s, 2H), 13.376 (s, 1H). (C22H18N4O4.1/2H2O) C, H, N. ESI-MS: m/z 400.9 [M−H]−.
Reaction SMILES: [CH2:1]([C:4]1([CH:25]([CH3:27])[CH3:26])[CH2:8][CH2:7][N:6]([CH2:9][C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([C:20]([F:23])([F:22])[F:21])[CH:11]=2)[C:5]1=[O:24])[CH:2]=C.CSC.CC(C)=[O:33]>>[F:21][C:20]([F:23])([F:22])[C:12]1[CH:11]=[C:10]([CH:15]=[C:14]([C:16]([F:19])([F:17])[F:18])[CH:13]=1)[CH2:9][N:6]1[CH2:7][CH2:8][C:4]([CH2:1][CH:2]=[O:33])([CH:25]([CH3:27])[CH3:26])[C:5]1=[O:24]
Reactant: C=CCC1(C(C)C)CCN(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)C1=O
Reactant: CC(C)=O
Solvent: CSC
Product: CC(C)C1(CC=O)CCN(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)C1=O
Temperature: 25 °C

Procedure:
A solution of 3-allyl-1-(3,5-bis(trifluoromethyl)-benzyl)-3-isopropylpyrrolidin-2-one (1.0 g, 2.54 mmol) in acetone (9 mL) was cooled to −78° C. O3 was bubbled through this solution until the color had changed from colorless to blue (30 min). At this point nitrogen gas was bubbled through the solution for 5 minutes, and dimethyl sulfide (1.88 mL, 25.4 mmol) was added. The solution was allowed to warm to room temperature over 2 h, and then concentrated in vacuo to yield impure 2-(1-(3,5-bis(trifluoromethyl)benzyl)-3-isopropyl-2-oxopyrrolidin-3-yl)acetaldehyde as a clear oil. Key non-solvent resonances in 1H-NMR (400 MHz, CDCl3) δ=9.81 (s, 1H), 8.0-7.8 (m, 3H), 5.2-5.0 (m, 1H), 4.7-4.5 (m, 1H), 3.4-3.1 (m, 2H), 2.2-1.8 (m, 5H), 1.0-0.8 (m, 6H).
Reaction SMILES: [Cl:1][C:2]1[C:3]([OH:9])=[CH:4][C:5](=[O:8])[NH:6][CH:7]=1.[CH2:10]([O:17][C:18]1[CH:26]=[CH:25][C:21]([C:22](Cl)=[O:23])=[CH:20][CH:19]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>N1C=CC=CC=1>[CH2:10]([O:17][C:18]1[CH:19]=[CH:20][C:21]([C:22]([O:9][C:3]2[C:2]([Cl:1])=[CH:7][NH:6][C:5](=[O:8])[CH:4]=2)=[O:23])=[CH:25][CH:26]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: O=c1cc(O)c(Cl)c[nH]1
Reactant: O=C(Cl)c1ccc(OCc2ccccc2)cc1
Solvent: c1ccncc1
Product: O=C(Oc1cc(=O)[nH]cc1Cl)c1ccc(OCc2ccccc2)cc1
Temperature: 25 °C
Yield: 10.5 %

Procedure:
A 3.00 g quantity of 5-chloro-4-hydroxy-2-pyridone was suspended in 100 ml of pyridine. To the suspension was added 5.59 g of 4-benzyloxybenzoyl chloride with stirring at room temperature. The reaction mixture was stirred at 90° C. for 1.5 hours. The solvent was distilled off and ethyl acetate was added to the residue. The mixture was stirred at room temperature overnight. The ethyl acetate layer was concentrated and the residue was subjected to silica gel column chromatography using as an eluent 2% methanol-chloroform, giving 770 mg of the title compound in a yield of 10.5%.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([C:12](=O)[C:13]([O:15]CCCCCC)=O)[CH:5]=[C:6]([N+:9]([O-:11])=[O:10])[C:7]=1[OH:8].[NH2:23]/[C:24](/[C:29]#[N:30])=[C:25](\[NH2:28])/[C:26]#[N:27]>C(O)C>[OH:15][C:13]1[N:28]=[C:25]([C:26]#[N:27])[C:24]([C:29]#[N:30])=[N:23][C:12]=1[C:4]1[CH:5]=[C:6]([N+:9]([O-:11])=[O:10])[C:7]([OH:8])=[C:2]([OH:1])[CH:3]=1
Reactant: N#C/C(N)=C(/N)C#N
Reactant: CCCCCCOC(=O)C(=O)c1cc(O)c(O)c([N+](=O)[O-])c1
Solvent: CCO
Product: N#Cc1nc(O)c(-c2cc(O)c(O)c([N+](=O)[O-])c2)nc1C#N

Procedure:
A solution of 4.0 g of n-hexyl 3,4-dihydroxy-5-nitrophenylglyoxylate and 1.5 g of diaminomaleonitrile in 35 ml of ethanol is heated to boiling under reflux for 24 hours. The alcohol is then distilled , the residue is dissolved in ether, washed with water, dried over sodium sulfate, filtered and evaporated. There is obtained 6-hydroxy-5-(3,4-dihydroxy-5-nitrophenyl)-2,3-pyrazinedicarbonitrile of m.p. >300° (from ether/methylene chloride).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([O:26][C@H:25]([CH2:27][O:28]C(=O)C)[C@@H:20]([O:21]C(=O)C)[C@H:15]([O:16]C(=O)C)[C@H:10]2[O:11]C(=O)C)[OH:9])=[CH:4][C:3]=1[CH2:32]Br.[F:34][C:35]1[CH:36]=[C:37](B(O)O)[CH:38]=[C:39]([F:43])[C:40]=1[O:41][CH3:42].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O.O.[Pd](Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@:8]2([O:26][C@H:25]([CH2:27][OH:28])[C@@H:20]([OH:21])[C@H:15]([OH:16])[C@H:10]2[OH:11])[OH:9])=[CH:4][C:3]=1[CH2:32][C:37]1[CH:36]=[C:35]([F:34])[C:40]([O:41][CH3:42])=[C:39]([F:43])[CH:38]=1
Reactant: CC(=O)OC[C@H]1OC(O)(c2ccc(Cl)c(CBr)c2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: COc1c(F)cc(B(O)O)cc1F
Agent: Cl[Pd]Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC(C)=O
Product: COc1c(F)cc(Cc2cc([C@@]3(O)O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)ccc2Cl)cc1F
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A stirred mixture of 1-chloro-4-(2,3,4,6-tetra-O-acetyl-D-glucopyranos-1-yl)-2-bromomethyl-benzene (0.30 g), 3,5-difluoro-4-methoxy-phenylboronic acid (0.21 g) and potassium carbonate (0.31 g) in acetone (3 mL) and water (1 mL) under argon is cooled in an ice-bath. Then palladium dichloride (5 mg) is added and the cooling bath is removed. The reaction mixture is stirred at ambient temperature overnight. Then brine is added and the resulting mixture is extracted with ethyl acetate. The combined extracts are dried over sodium sulfate, and the solvent is removed in vacuo. The residue is taken up in methanol (5 mL) aqueous potassium hydroxide solution (1 mL, 4 mol/L) is added. The solution is stirred at ambient temperature for 0.5 h and then neutralized with 1 M hydrochloric acid. The methanol is evaporated, and the residue is diluted with brine and extracted with ethyl acetate. The organic extracts are dried over sodium sulfate, and the solvent is removed. The residue is chromatographed on silica gel (dichloromethane/methanol 1:0->9:1).
Reaction SMILES: [CH3:1][C:2]([CH3:17])([O:4][C:5]([NH:7][CH:8]([C:12]([CH3:16])([CH3:15])[CH:13]=[CH2:14])[C:9]([OH:11])=O)=[O:6])[CH3:3].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.[CH2:49]([NH:52][CH2:53][C:54]1[CH:59]=[CH:58][C:57]([O:60][CH3:61])=[CH:56][C:55]=1[O:62][CH3:63])[CH:50]=[CH2:51]>CN(C)C=O>[C:2]([O:4][C:5](=[O:6])[NH:7][CH:8]([C:9](=[O:11])[N:52]([CH2:49][CH:50]=[CH2:51])[CH2:53][C:54]1[CH:59]=[CH:58][C:57]([O:60][CH3:61])=[CH:56][C:55]=1[O:62][CH3:63])[C:12]([CH3:16])([CH3:15])[CH:13]=[CH2:14])([CH3:1])([CH3:3])[CH3:17]
Reactant: C=CC(C)(C)C(NC(=O)OC(C)(C)C)C(=O)O
Reactant: C=CCNCc1ccc(OC)cc1OC
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: C=CCN(Cc1ccc(OC)cc1OC)C(=O)C(NC(=O)OC(C)(C)C)C(C)(C)C=C
Reaction time: 8 h
Yield: 89.3 %

Procedure:
2-[[(1,1-Dimethylethoxy)carbonyl]amino]-3,3-dimethyl-4-pentenoic acid (322 mg, 1.32 mmol; Synthesis see Bartlett, Paul A.; Barstow, James F. Journal of Organic Chemistry (1982), 47(20), 3933-41) was dissolved in dimethylformamide (6 ml) and activated with the coupling reagent TATU (469 mg, 1.46 mmol) and Hünig's base (376 mg, 2.91 mmol) for 2 min. Allyl-(2,4-dimethoxy-benzyl)-amine (274 mg, 1.32 mmol) dissolved in dimethylformamide (2 ml) was added and the mixture was stirred overnight. The solvent was evaporated and the residue was dissolved in ethyl acetate, washed with saturated NaHCO3 solution, 1 M KHSO4 solution and brine. After drying with magnesiumsulfate the organic layer was concentrated and purified by flash chromatography (heptane/ethyl acetate=2:1) to yield 510 mg (89%) of {1-[allyl-(2,4-dimethoxy-benzyl)-carbamoyl]-2,2-dimethyl-but-3-enyl}-carbamic acid tert-butyl ester; MS: m/e=433.6 (MH+), 450.6 (M+NH4+).
Reaction SMILES: [Si:1]([O:8][C@H:9]1[CH2:13][C@@H:12](O)[C:11](=[CH2:15])[C@@H:10]1[CH2:16][O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Cl:25][C:26]1[N:34]=[C:33]([NH2:35])[N:32]=[C:31]2[C:27]=1[NH:28][CH:29]=[N:30]2.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[Si:1]([O:8][C@H:9]1[CH2:13][C@H:12]([N:30]2[CH:29]=[N:28][C:27]3[C:31]2=[N:32][C:33]([NH2:35])=[N:34][C:26]=3[Cl:25])[C:11](=[CH2:15])[C@@H:10]1[CH2:16][O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:19])[CH3:20])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3]
Reactant: C=C1[C@H](O)C[C@H](O[Si](C)(C)C(C)(C)C)[C@H]1CO[Si](C)(C)C(C)(C)C
Reactant: Nc1nc(Cl)c2[nH]cnc2n1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: C=C1[C@H](CO[Si](C)(C)C(C)(C)C)[C@@H](O[Si](C)(C)C(C)(C)C)C[C@@H]1n1cnc2c(Cl)nc(N)nc21
Temperature: -23 °C
Reaction time: 3.5 h
Yield: 58.2 %

Procedure:
370 mg (1.0 mmol) (1R,3R,4S)-4-(tert-butyldimethylsilyloxy)-3-[(tert-butyldimethylsilyloxy)methyl]-2-methylene-cyclopentanol (Compound 4a, R1═R2=t-BuMe2Si), 338 mg (2.0 mmol) 6-chloro-2-aminopurine (Compound 23) and 524 mg Ph3P (2.0 mmol) were placed into 20 ml round bottom flask, to which 5 ml anhydrous THF was then added. The mixture was cooled to −23° C., to which a solution of 350 mg DEAD (1.0 mmol)/5 ml THF was added dropwise. After addition was completed, the reaction mixture was stirred at −23° C. for 3.5 hours, warmed to room temperature and stirred at room temperature overnight. Subsequently THF was evaporated off under reduced pressure. 10 ml t-BuOMe was added to the residue. The mixture was stirred for 5 minutes, to which 15 ml n-hexane was added. The mixture was maintained standing for 5 hours, and filtered to remove insoluble substance. The filtrate was purified with column chromatography, eluting with petroleum ether/EtOAc (3/1 (v/v)), to afford 305 mg (59%) of title compound as light yellow oil.
Reaction SMILES: [NH2:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:11][CH3:12])[CH:9]=2)[CH:4]=[CH:3]1.CN(C)[C:15]1[O:16][C:17](=[O:25])[CH:18]=[C:19]([C:21]([F:24])([F:23])[F:22])[N:20]=1.C(O)(=O)C>O>[CH3:12][O:11][C:8]1[CH:9]=[C:10]2[C:5]([CH:4]=[CH:3][N:2]2[N:1]2[C:17](=[O:25])[CH:18]=[C:19]([C:21]([F:24])([F:23])[F:22])[NH:20][C:15]2=[O:16])=[CH:6][CH:7]=1
Reactant: CN(C)c1nc(C(F)(F)F)cc(=O)o1
Reactant: COc1ccc2ccn(N)c2c1
Solvent: CC(=O)O
Solvent: O
Product: COc1ccc2ccn(-n3c(=O)cc(C(F)(F)F)[nH]c3=O)c2c1
Yield: 57.3 %

Procedure:
A mixture of 0.2 g 1A, 0.268 g 2-dimethylamino-4-trifluoromethyl-1,3-oxazin-6-one (obtained according to M.-A. Decock-Plancquaert et al., Bull. Soc. Chim. Belg. 101 (4) 313-321 (1992)) and 10 ml acetic acid is refluxed for 4 hours. The mixture is poured into water, extracted and chromatographed to yield 0.23 g of 1B as an oil.
Reaction SMILES: [CH3:1][CH2:2][O:3][C:4]([CH2:6][C:7]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=O)=[O:5].[CH:15]1([NH2:18])[CH2:17][CH2:16]1>O>[CH:15]1([NH:18][C:7]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:6][C:4]([O:3][CH2:2][CH3:1])=[O:5])[CH2:17][CH2:16]1
Reactant: CCOC(=O)CC(=O)CC(=O)OCC
Reactant: NC1CC1
Solvent: O
Product: CCOC(=O)C=C(CC(=O)OCC)NC1CC1
Temperature: 25 °C
Reaction time: 18 h
Yield: 95.1 %

Procedure:
To 30.33 g (0.15 mol) of diethyl acetonedicarboxylate was added dropwise 11.8 g (0.19 mol) of cyclopropylamine at such a rate that reaction temperature was kept below 48° C. The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was poured into H2O, extracted twice with ether, dried (MgSO4) and concentrated in vacuo affording 34.42 g of a light yellow oil. Crude was kugelrohr distilled at 53 Pa and collected at a pot temperature of 102°-104° C. to give 23.73 g (66%) of enamine diester as a light yellow oil, nD25 1.5025.
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6].CC([O-])(C)C.[K+].Br[CH2:14][C:15]1[CH:16]=[C:17]([C:21]2[CH:25]=[C:24]([CH2:26][CH:27]([CH3:29])[CH3:28])[S:23][C:22]=2[S:30]([NH:33][C:34]([CH3:37])([CH3:36])[CH3:35])(=[O:32])=[O:31])[CH:18]=[CH:19][CH:20]=1>CS(C)=O.C(Cl)Cl>[N:1]1([CH2:14][C:15]2[CH:16]=[C:17]([C:21]3[CH:25]=[C:24]([CH2:26][CH:27]([CH3:29])[CH3:28])[S:23][C:22]=3[S:30]([NH:33][C:34]([CH3:36])([CH3:35])[CH3:37])(=[O:31])=[O:32])[CH:18]=[CH:19][CH:20]=2)[CH2:5][CH2:4][CH2:3][C:2]1=[O:6]
Reactant: O=C1CCCN1
Reactant: CC(C)Cc1cc(-c2cccc(CBr)c2)c(S(=O)(=O)NC(C)(C)C)s1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CS(C)=O
Product: CC(C)Cc1cc(-c2cccc(CN3CCCC3=O)c2)c(S(=O)(=O)NC(C)(C)C)s1
Temperature: 25 °C
Reaction time: 1 h
Yield: 77 %

Procedure:
To a solution of 2-pyrrolidinone (26.5 mg, 0.312 mmol) in DMSO (1 mL) and t-BuOK (48.9 mg, 0.436 mmol), that had been stirred for 40 min at ambient temperature, was added a solution of 3-(3-bromomethylphenyl)-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide (92.3 mg, 0.208 mmol; see Example 1(e)) in DMSO (1 mL) dropwise. The reaction mixture was stirred for 1 h at ambient temperature and then diluted with CH2Cl2 (15 mL). The organic layer was washed with water, dried (over anhydrous MgSO4), concentrated in vacuo, and the residue purified by flash chromatography using MeOH:CH2Cl2 (2:98) as eluent to give the sub-title compound in 77% yield as a colourless syrup (72.3 mg, 0.161 mmol).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:12])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.[F:13][C:14]1[CH:20]=[CH:19][C:17]([NH2:18])=[CH:16][CH:15]=1>C(OCC)(=O)C>[Cl:12][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:18][C:17]3[CH:19]=[CH:20][C:14]([F:13])=[CH:15][CH:16]=3)=[CH:3][CH:4]=[N:5]2)=[CH:10][CH:9]=1
Reactant: Clc1ccc2c(Cl)ccnc2c1
Reactant: Nc1ccc(F)cc1
Solvent: CCOC(C)=O
Product: Fc1ccc(Nc2ccnc3cc(Cl)ccc23)cc1
Temperature: 160 °C
Yield: 46.1 %

Procedure:
To 2.0 g of 4,7-dichloroquinoline was added 2.24 g of 4-fluoroaniline, and the mixture was heated with stirring to 160° C. After a few minutes at this temperature, the mixture smoked and the melt solidified. The solid was allowed to cool and was then dissolved in ethyl acetate and washed to remove the aniline. The organic layer was dried over MgSO4 and then solvent was removed using reduced pressure. The residue was recrystallized in heptane to yield 1.27 g of 7-chloro-N-(4-fluorophenyl)-4-quinolinamine. M.P. 214°-16° C. (46.1% yield).