Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CN(C)C=O.[CH3:6][C:7]1[CH:8]=[C:9]2[C:18](=[CH:19][CH:20]=1)[C:17](=[O:21])[C:16]1[CH2:15][CH:14]([C:22]([NH2:24])=O)[CH2:13][CH2:12][C:11]=1[O:10]2.S(Cl)(Cl)=O>O>[CH3:6][C:7]1[CH:8]=[C:9]2[C:18](=[CH:19][CH:20]=1)[C:17](=[O:21])[C:16]1[CH2:15][CH:14]([C:22]#[N:24])[CH2:13][CH2:12][C:11]=1[O:10]2
Reactant: Cc1ccc2c(=O)c3c(oc2c1)CCC(C(N)=O)C3
Solvent: O=S(Cl)Cl
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ccc2c(=O)c3c(oc2c1)CCC(C#N)C3
Reaction time: 0.5 h
Yield: 43 %

Procedure:
To 15 ml of a dimethyl formamide suspension solution containing 1.0 g of 6-methyl-1,2,3,4-tetrahydro-9-oxo-xanthene-2-carboxylic acid amide was amide was added dropwise 1.19 g of thionyl chloride at 0° C., and the mixture was stirred for 30 minutes. The resulting mixture was then poured into iced water and decomposed. The separated powder was recrystallized from acetone to obtain 0.40 g (yield: 41%) of 6-methyl-1,2,3,4-tetrahydro-9-oxo-xanthene-2-carbonitrile as a white powder having a melting point of 176° to 178° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[CH:13]=[CH:14][C:15](OCC)=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)Cl.B(F)(F)F.CCOCC.CC(C[AlH]CC(C)C)C>CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[CH:13]=[CH:14][CH2:15][OH:16])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CCOC(=O)C=CC1CCCN1C(=O)OC(C)(C)C
Agent: CC(C)C[AlH]CC(C)C
Agent: FB(F)F
Solvent: CCOC(C)=O
Solvent: ClCCl
Solvent: CCOCC
Product: CC(C)(C)OC(=O)N1CCCC1C=CCO
Temperature: -78 °C
Yield: 79.2 %

Procedure:
A 2 L, 3-necked round bottomed flask equipped with an overhead stirred was charged with 14 (67 g, 0.20 mol) and DCM (400 mL). The solution was cooled to −78° C. To this solution was slowly added boron trifluoride etherate (30 mL, 0.20 mol). The reaction mixture was stirred for 30 min. DIBAL (1 M in DCM, 600 mL, 0.6 mol) was added at a moderate rate. The solution was stirred at −78° C. for 2 h and then treated with EtOAc (100 mL) over 30 min to discharge remaining reagent. The reaction mixture was allowed to warm to −5° C. The reaction mixture was CAREFULLY quenched by the dropwise addition of 1 M HCl. The reaction mixture was diluted with DCM and H2O and made acidic to dissolve aluminum salts. The layers were separated and the organic phase was washed successively with dilute aqueous HCl, water, and brine. The DCM layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography (SiO2, 25% to 80% EtOAc/hexane) to afford 15 as a yellow oil (36 g, 79%). [TLC analysis, 1:1 hexane/EtOAc, Rf(14)=0.8; Rf(15)=0.2]. 1H NMR (CDCl3, 300 MHz) δ5.73-5.52 (m, 2H), 4.39-4.16 (m, 1H), 4.15-4.04 (m, 2H), 3.46-3.25 (m, 2H), 2.92 (br s, 1H), 2.08-1.93 (m, 1H), 1.92-1.79 (m, 2H), 1.78-1.62 (m, 1H), 1.42 (s, 9H) ppm.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([O:10][C:11]2[CH:16]=[CH:15][C:14](Cl)=[C:13]([N+:18]([O-:20])=[O:19])[CH:12]=2)[CH3:9])=[CH:4][CH:3]=1.[SH:21][C:22]1[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([O:10][C:11]2[CH:16]=[CH:15][C:14]([S:21][C:22]3[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=3)=[C:13]([N+:18]([O-:20])=[O:19])[CH:12]=2)[CH3:9])=[CH:4][CH:3]=1
Reactant: CC(Oc1ccc(Cl)c([N+](=O)[O-])c1)c1ccc(Br)cc1
Reactant: Oc1ccc(S)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(Oc1ccc(Sc2ccc(O)cc2)c([N+](=O)[O-])c1)c1ccc(Br)cc1
Temperature: 25 °C
Yield: 68.2 %

Procedure:
The product from Example 44B (1.15 g, 3.22 mmol) was reacted with 4-mercapto-phenol (403 mg, 3.22 mmol) and K2CO3 (890 mg, 6.44 mmol) in 25 mL of DMF at 80° C. for 18 h. Cooled to room temperature and poured into water. Extracted with CH2Cl2 and washed several times with water. Dried over Na2SO4, filtered and concentrated under vacuum giving the title compound (980 mg, 68%).
Reaction SMILES: [H-].[Na+].[OH:3][CH:4]1[CH2:9][O:8][CH:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[O:6][CH2:5]1.CN(C)C=O.Cl[C:22]1[N:31]=[C:30]([NH:32][CH2:33][C:34]2[CH:39]=[CH:38][C:37]3[O:40][CH2:41][O:42][C:36]=3[CH:35]=2)[C:29]2[C:24](=[CH:25][CH:26]=[C:27]([Cl:43])[CH:28]=2)[N:23]=1>O>[C:10]1([CH:7]2[O:6][CH2:5][CH:4]([O:3][C:22]3[N:31]=[C:30]([NH:32][CH2:33][C:34]4[CH:39]=[CH:38][C:37]5[O:40][CH2:41][O:42][C:36]=5[CH:35]=4)[C:29]4[C:24](=[CH:25][CH:26]=[C:27]([Cl:43])[CH:28]=4)[N:23]=3)[CH2:9][O:8]2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: OC1COC(c2ccccc2)OC1
Reactant: Clc1ccc2nc(Cl)nc(NCc3ccc4c(c3)OCO4)c2c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Clc1ccc2nc(OC3COC(c4ccccc4)OC3)nc(NCc3ccc4c(c3)OCO4)c2c1
Temperature: 80 °C
Yield: 27.8 %

Procedure:
100 mg of sodium hydride was added to a mixture comprising 300 mg of 5-hydroxy-2-phenyl-1,3-dioxane and 5 ml of dimethylformamide. The obtained mixture was heated to 80° C. After the bubbling had been discontinued, 300 mg of 2,6-dichloro-4-(3,4-methylenedioxybenzyl)aminoquinazoline was added in a crystalline state. The obtained mixture was heated at 140° C. for 2 hours and cooled, followed by the addition of water. The obtained mixture was extracted with ethyl acetate. The extract was purified by silica gel column chromatography using an ethyl acetate/benzene mixture to give 118 mg of 2-(2-phenyl-1,3-dioxan-5-yl)oxy-4-(3,4-methylenedioxybenzyl)amino-6-chloroquinazoline. 100 mg of this compound was hydrolyzed with concentrated hydrochloric acid/ethanol by a conventional process to give 60 mg of the title compound through rearrangement.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[CH:11]=[C:10]([C:24]([F:27])([F:26])[F:25])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[S:28]([C:32]1[CH:33]=[N:34][CH:35]=[C:36](B(O)O)[CH:37]=1)(=[O:31])(=[O:30])[NH2:29]>>[F:25][C:24]([F:27])([F:26])[C:10]1[N:9]=[C:8]([C:4]2[CH:3]=[C:2]([C:36]3[CH:37]=[C:32]([S:28]([NH2:29])(=[O:31])=[O:30])[CH:33]=[N:34][CH:35]=3)[CH:7]=[CH:6][CH:5]=2)[CH:13]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)[CH:11]=1
Reactant: FC(F)(F)c1ccc(-c2cc(-c3cccc(Br)c3)nc(C(F)(F)F)c2)cc1
Reactant: NS(=O)(=O)c1cncc(B(O)O)c1
Product: NS(=O)(=O)c1cncc(-c2cccc(-c3cc(-c4ccc(C(F)(F)F)cc4)cc(C(F)(F)F)n3)c2)c1

Procedure:
The title compound was prepared 2-(3-bromo-phenyl)-6-trifluoromethyl-4-(4-trifluoromethyl-phenyl)-pyridine (example E.81) (0.20 g, 0.448 mmol) and 3-sulfamoyl-pyridine-5-boronic acid (example F.3) (0.100 g, 0.488 mmol) according to the general procedure VI. Obtained as a white solid (0.035 g, 15%). MS (ISP) 522.2 [(M+H)+]; mp 240° C.
Reaction SMILES: [C:1](OC(=O)C)(=[O:3])[CH3:2].[Br:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](=[O:19])[N:14]([CH2:20][C:21]1[CH:26]=[CH:25][C:24]([S:27]([NH2:30])(=[O:29])=[O:28])=[CH:23][CH:22]=1)[C:13]([C:31](=[O:34])[CH2:32][CH3:33])=[C:12]2[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>>[Br:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](=[O:19])[N:14]([CH2:20][C:21]1[CH:22]=[CH:23][C:24]([S:27]([NH:30][C:1](=[O:3])[CH3:2])(=[O:28])=[O:29])=[CH:25][CH:26]=1)[C:13]([C:31](=[O:34])[CH2:32][CH3:33])=[C:12]2[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1
Reactant: CCC(=O)c1c(-c2ccccc2)c2cc(Br)ccc2c(=O)n1Cc1ccc(S(N)(=O)=O)cc1
Reactant: CC(=O)OC(C)=O
Product: CCC(=O)c1c(-c2ccccc2)c2cc(Br)ccc2c(=O)n1Cc1ccc(S(=O)(=O)NC(C)=O)cc1

Procedure:
The present compound was synthesized by a method similar to that in Example 515 and using acetic anhydride and 4-(6-bromo-1-oxo-4-phenyl-3-propionyl-1H-isoquinolin-2-ylmethyl)benzenesulfonamide. 1H NMR (CDCl3) δ: 0.49 (3H, t, J=7.2 Hz), 1.71 (2H, q, J=7.2 Hz), 2.00 (3H, s), 5.36 (2H, s), 7.23-7.30 (2H, m), 7.39 (2H, d, J=8.4 Hz), 7.43-7.52 (4H, m), 7.68 (1H, dd, J=2.1, 8.7 Hz), 7.96 (2H, d, J=8.4 Hz), 8.38 (1H, d, J=8.7 Hz). HPLC analysis: purity 99.4% (retention time: 4.50 min). MS (ESI+): 567 (M+H), 569.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[CH:11]=[C:10]([C:12]3[CH:17]=[N:16][N:15]4[C:18]([C:21]5[CH:22]=[C:23]([NH:27][C:28]([NH:30][CH2:31][C:32]([F:35])([F:34])[F:33])=[O:29])[CH:24]=[CH:25][CH:26]=5)=[CH:19][N:20]=[C:14]4[CH:13]=3)[CH:9]=[N:8]2)[CH2:3][CH2:2]1.[N:36]1([C:41](Cl)=[O:42])[CH2:40][CH2:39][CH2:38][CH2:37]1>>[N:36]1([C:41]([N:1]2[CH2:6][CH2:5][CH:4]([N:7]3[CH:11]=[C:10]([C:12]4[CH:17]=[N:16][N:15]5[C:18]([C:21]6[CH:22]=[C:23]([NH:27][C:28]([NH:30][CH2:31][C:32]([F:33])([F:35])[F:34])=[O:29])[CH:24]=[CH:25][CH:26]=6)=[CH:19][N:20]=[C:14]5[CH:13]=4)[CH:9]=[N:8]3)[CH2:3][CH2:2]2)=[O:42])[CH2:40][CH2:39][CH2:38][CH2:37]1
Reactant: O=C(Cl)N1CCCC1
Reactant: O=C(NCC(F)(F)F)Nc1cccc(-c2cnc3cc(-c4cnn(C5CCNCC5)c4)cnn23)c1
Product: O=C(NCC(F)(F)F)Nc1cccc(-c2cnc3cc(-c4cnn(C5CCN(C(=O)N6CCCC6)CC5)c4)cnn23)c1

Procedure:
This compound was prepared by using procedures analogous to those described for the synthesis of Example 30 (Step 6) starting from N-{3-[7-(1-piperidin-4-yl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-3-yl]phenyl}-N′-(2,2,2-trifluoroethyl)urea and 1-pyrrolidinecarbonyl chloride (Aldrich, Cat. No. 206350). LCMS (M+H)+: m/z=582.3.
Reaction SMILES: [CH3:1][N:2]([CH3:28])[C:3]1[CH:4]=[C:5]([CH:25]=[CH:26][CH:27]=1)[O:6][C:7]1[CH:8]=[CH:9][C:10]([N+:22]([O-])=O)=[C:11]([N:13]([CH3:21])[C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH:12]=1>[Pd].CO>[NH2:22][C:10]1[CH:9]=[CH:8][C:7]([O:6][C:5]2[CH:25]=[CH:26][CH:27]=[C:3]([N:2]([CH3:1])[CH3:28])[CH:4]=2)=[CH:12][C:11]=1[N:13]([CH3:21])[C:14](=[O:20])[O:15][C:16]([CH3:17])([CH3:18])[CH3:19]
Reactant: CN(C)c1cccc(Oc2ccc([N+](=O)[O-])c(N(C)C(=O)OC(C)(C)C)c2)c1
Agent: [Pd]
Solvent: CO
Product: CN(C)c1cccc(Oc2ccc(N)c(N(C)C(=O)OC(C)(C)C)c2)c1
Yield: 82.6 %

Procedure:
In a similar manner to that described in Reference Example 7, a reaction was carried out using t-butyl N-[5-(3-dimethylaminophenoxy)-2-nitrophenyl]-N-methylcarbamate (2.14 g), palladium on carbon (10%, 2.14 g) and methanol (40 ml) and the reaction mixture was purified to give the title compound (1.63 g).
Reaction SMILES: Cl[C:2]1(Cl)[C@@H:6]([CH2:7]Cl)[C@H:5]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[NH:4][C:3]1=[O:16].C([SnH](CCCC)CCCC)CCC.[F-].[K+].C(OCC)(=O)C>C1(C)C=CC=CC=1.CC(N=NC(C#N)(C)C)(C#N)C>[CH3:7][C@H:6]1[C@H:5]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[NH:4][C:3](=[O:16])[CH2:2]1
Reactant: O=C1N[C@@H](Cc2ccccc2)[C@H](CCl)C1(Cl)Cl
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Agent: CCCC[SnH](CCCC)CCCC
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: C[C@@H]1CC(=O)N[C@H]1Cc1ccccc1
Yield: 32.1 %

Procedure:
A solution of the product of Example 61 (1.3 g), tributyltin hydride (3.85 g) and AIBN (16 mg) in toluene (50 mL) was refluxed for 4 hours. The reaction mixture was treated with a solution of KF (20%, 40 mL) and ethyl acetate (100 mL), filtered, concentrated and chromatographed to yield the title material (270 mg).
Reaction SMILES: Cl[C:2]1[N:3]=[N:4][C:5]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)=[CH:6][CH:7]=1.[NH2:14][CH:15]([CH3:18])[CH2:16][OH:17]>>[N:10]1[CH:11]=[CH:12][CH:13]=[C:8]([C:5]2[N:4]=[N:3][C:2]([NH:14][CH:15]([CH3:18])[CH2:16][OH:17])=[CH:7][CH:6]=2)[CH:9]=1
Reactant: CC(N)CO
Reactant: Clc1ccc(-c2cccnc2)nn1
Product: CC(CO)Nc1ccc(-c2cccnc2)nn1
Temperature: 130 °C

Procedure:
A mixture of 5 g of 3-chloro-6-(3-pyridinyl)pyridazine and 30 ml of 2-amino-1-propanol is heated at 130° C. for 24 hours and the volatiles removed by bulb to bulb distillation under high vacuum to obtain the product 2-[[6-(3-pyridinyl)-3-pyridazinyl]amino]-1-propanol. As for Example 5, the preceding product is reacted with thionyl chloride and the obtained product is ring closed with potassium carbonate in ethanol to give 2,3-dihydro-2-methyl-6-(3-pyridinyl)imidazo[1,2-b]pyridazine which is dehydrogenated with lead tetraacetate to give 2-methyl-6-(3-pyridinyl)imidazo[1,2-b]pyridazine.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:11][C:10]([CH3:13])([CH3:12])[C@@H:9]([OH:14])[C@H:8]([N:15]3[CH2:19][C:18]([O:20][CH3:21])=[CH:17][C:16]3=[O:22])[C:7]=2[CH:23]=1)#[N:2].C(O)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.CS(O)(=O)=O>>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:11][C:10]([CH3:13])([CH3:12])[C@@H:9]([OH:14])[C@H:8]([N:15]3[CH2:19][C:18]([O:20][CH2:21][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)=[CH:17][C:16]3=[O:22])[C:7]=2[CH:23]=1)#[N:2]
Reactant: COC1=CC(=O)N([C@@H]2c3cc(C#N)ccc3OC(C)(C)[C@H]2O)C1
Reactant: OCc1ccccc1
Agent: CS(=O)(=O)O
Product: CC1(C)Oc2ccc(C#N)cc2[C@@H](N2CC(OCc3ccccc3)=CC2=O)[C@@H]1O

Procedure:
Alternatively, a mixture of 6-cyano-3,4-dihydro-2,2-dimethyl-trans-3-hydroxy-4-(4-methoxy-2-oxo-3-pyrrolin-1-yl)-2H-1-benzopyran (0.7 g), benzyl alcohol (0.92 ml) and methanesulfonic acid (0.01 g) was refluxed for 2 hours in the presence of 3A molecular sieves. After cooling the molecular sieves were filtered off, the filtrate stirred with diethylether, the insoluble product filtered off and washed twice with diethylether, to give 6-cyano-3,4-dihydro-2,2-dimethyl-trans-3-hydroxy-4-(4-benzyloxy-2-oxo-3-pyrrolin-1-yl)-2H-1-benzopyran, m.p. 248° C.
Reaction SMILES: [C:1]([C:3]1([NH:6][C:7]([C@@H:9]2[CH2:13][C@@H:12]([S:14]([C:17]3[CH:22]=[CH:21][C:20](Br)=[CH:19][C:18]=3[C:24]([F:27])([F:26])[F:25])(=[O:16])=[O:15])[CH2:11][C@H:10]2[C:28]([N:30]2[CH2:33][C:32]([F:35])([F:34])[CH2:31]2)=[O:29])=[O:8])[CH2:5][CH2:4]1)#[N:2].[N:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][C:37]=1[CH3:45]>>[C:1]([C:3]1([NH:6][C:7]([C@@H:9]2[CH2:13][C@@H:12]([S:14]([C:17]3[CH:22]=[CH:21][C:20]([C:39]4[CH:40]=[CH:41][N:36]=[C:37]([CH3:45])[CH:38]=4)=[CH:19][C:18]=3[C:24]([F:27])([F:26])[F:25])(=[O:16])=[O:15])[CH2:11][C@H:10]2[C:28]([N:30]2[CH2:33][C:32]([F:35])([F:34])[CH2:31]2)=[O:29])=[O:8])[CH2:5][CH2:4]1)#[N:2]
Reactant: N#CC1(NC(=O)[C@@H]2C[C@@H](S(=O)(=O)c3ccc(Br)cc3C(F)(F)F)C[C@H]2C(=O)N2CC(F)(F)C2)CC1
Reactant: Cc1cc(B(O)O)ccn1
Product: Cc1cc(-c2ccc(S(=O)(=O)[C@@H]3C[C@@H](C(=O)NC4(C#N)CC4)[C@H](C(=O)N4CC(F)(F)C4)C3)c(C(F)(F)F)c2)ccn1

Procedure:
The title compound was prepared in analogy to Example 120 using (1R,2R,4R)-4-(4-Bromo-2-trifluoromethyl-benzenesulfonyl)-2-(3,3-difluoro-azetidine-1-carbonyl)-cyclopentanecarboxylic acid (1-cyano-cyclopropyl)-amide (Example 117) and 2-picoline-4-boronic acid. Yellow solid. MS (EI): 597.1 (M+H)+.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:8]([S:11]([N:14]2[CH:27]([CH3:28])[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]2=3)(=[O:13])=[O:12])=[CH:7][C:3]=1[C:4](O)=[O:5]>O1CCCC1>[OH:5][CH2:4][C:3]1[CH:7]=[C:8]([S:11]([N:14]2[CH:27]([CH3:28])[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]2=3)(=[O:12])=[O:13])[CH:9]=[CH:10][C:2]=1[OH:1]
Reactant: CC1c2ccccc2-c2ccccc2N1S(=O)(=O)c1ccc(O)c(C(=O)O)c1
Solvent: C1CCOC1
Product: CC1c2ccccc2-c2ccccc2N1S(=O)(=O)c1ccc(O)c(CO)c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 35.4 %

Procedure:
A stirred solution of crude 2-hydroxy-5-[(6-methylphenanthridin-5(6H)-yl)sulfonyl]benzoic acid (1.75 g, 4.43 mmol) in anhydrous tetrahydrofuran (20 mL) was treated drop-wise at room temperature under nitrogen via syringe with 10 M borane-methyl sulfide complex (1.5 mL, 15 mmol). After stirring four hours at room temperature, the reaction was quenched with methanol (20 mL), concentrated in vacuo, diluted with water, and extracted with ethyl acetate. The organic phase was washed sequentially with an aqueous solution of potassium carbonate, water, a saturated, aqueous, sodium chloride solution, a 1 N hydrochloric acid solution, and water. The organic phase was dried over anhydrous sodium sulfate, filtered through a short column of silica gel, and eluted with ethyl acetate. The ethyl acetate phase was evaporated in vacuo to a crude oil (1.2 g). The crude oil was purified by preparative chromatography on a Biotage® 40 Mi column of pre-packed silica gel (90 g) with gradient elution of between 10% to 55% methyl tert-butyl ether in hexane at a flow rate of 50 mL/min; and afforded, after evaporation of the solvent, a colorless oil (0.687 g. 1.8 mmol). Crystallization of the colorless oil from diethyl ether yielded the title compound (0.6 g, 1.57 mmol, 35%) as a homogeneous, colorless, crystalline, solid, m.p. 182-184° C.;
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:12]2([C:35]([F:38])([F:37])[F:36])[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([N:25]4[CH2:29][C:28](=[O:30])[NH:27][CH2:26]4)=[O:24])=[C:19]([C:31]([F:34])([F:33])[F:32])[CH:18]=3)[CH2:13]2)[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[H-].[Na+].[F:41][C:42]([F:47])([F:46])[CH2:43][CH2:44]I.CC#N>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2([C:35]([F:36])([F:37])[F:38])[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([N:25]4[CH2:29][C:28](=[O:30])[N:27]([CH2:44][CH2:43][C:42]([F:47])([F:46])[F:41])[CH2:26]4)=[O:24])=[C:19]([C:31]([F:33])([F:34])[F:32])[CH:18]=3)[CH2:13]2)[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1
Reactant: FC(F)(F)CCI
Reactant: O=C1CN(C(=O)c2ccc(C3=NOC(c4cc(Cl)cc(C(F)(F)F)c4)(C(F)(F)F)C3)cc2C(F)(F)F)CN1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CC#N
Product: O=C1CN(C(=O)c2ccc(C3=NOC(c4cc(Cl)cc(C(F)(F)F)c4)(C(F)(F)F)C3)cc2C(F)(F)F)CN1CCC(F)(F)F
Reaction time: 8 h

Procedure:
Into a 50-mL round-bottom flask, was placed a solution of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl)carbonyl]imidazolidin-4-one (80 mg, 0.14 mmol, 1.00 equiv) in N,N-dimethylformamide (5 ml), sodium hydride (11 mg, 0.28 mmol, 2.00 equiv, 60%), 1,1,1-trifluoro-3-iodopropane (153 mg, 0.68 mmol, 5.00 equiv). The resulting solution was stirred overnight at r t. The reaction was then quenched by the addition of 10 mL of water. The resulting solution was extracted with 2×10 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3×10 mL of brine. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:1). This resulted in 17.8 mg (19%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl)carbonyl]-3-(3,3,3-trifluoropropyl)imidazolidin-4-one as a light yellow solid. (ES, m/z): [M+CH3CN]+ 711.0; 1H NMR (300 MHz, CD3OD): δ8.12-8.22 (m, 2H), 7.99 (s, 1H), 7.89 (d, J=5.4 Hz, 2H), 7.71 (d, J=5.1 Hz, 1H), 5.12 (s, 1H), 4.70 (s, 1H), 4.16-4.47 (m, 3H), 3.86 (s, 1H), 3.57-3.74 (m, 2H), 2.39-2.67 (m, 2H).
Reaction SMILES: CS(O[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]2[C:17]3[C:18]([O:22][CH3:23])=[N:19][CH:20]=[CH:21][C:16]=3[N:15]([C:24]3[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=3[F:31])[N:14]=2)[CH:8]=1)(=O)=O.[NH:32]1[CH2:36][CH2:35][CH2:34][CH2:33]1.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>CN(C=O)C>[F:31][C:25]1[CH:26]=[CH:27][CH:28]=[C:29]([F:30])[C:24]=1[N:15]1[C:16]2[CH:21]=[CH:20][N:19]=[C:18]([O:22][CH3:23])[C:17]=2[C:13]([C:9]2[CH:10]=[CH:11][CH:12]=[C:7]([CH2:6][N:32]3[CH2:36][CH2:35][CH2:34][CH2:33]3)[CH:8]=2)=[N:14]1
Reactant: COc1nccc2c1c(-c1cccc(COS(C)(=O)=O)c1)nn2-c1c(F)cccc1F
Reactant: C1CCNC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: COc1nccc2c1c(-c1cccc(CN3CCCC3)c1)nn2-c1c(F)cccc1F
Temperature: 60 °C
Reaction time: 4 h

Procedure:
To a solution of 3-(1-(2,6-difluorophenyl)-4-methoxy-1H-pyrazolo[4,3-c]pyridin-3-yl)benzyl methanesulfonate (100 mg) obtained in Step B of Example 258 and pyrrolidine (0.028 mL) in DMF (3 mL) was added triethylamine (0.047 mL) at room temperature, and the mixture was stirred at 60° C. for 4 hr. To the reaction mixture was added saturated aqueous sodium hydrogencarbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (basic silica gel, ethyl acetate/hexane) to give the title compound (70 mg).
Reaction SMILES: C1(O[C:8](=[S:20])[NH:9][C:10]2[C:11]([O:18][CH3:19])=[N:12][C:13]([CH3:17])=[C:14]([CH3:16])[CH:15]=2)C=CC=CC=1.[CH3:21][O:22][C:23]1[CH:24]=[C:25]([N:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)[CH:26]=[C:27]([O:29][CH3:30])[CH:28]=1>>[CH3:16][C:14]1[CH:15]=[C:10]([NH:9][C:8]([N:34]2[CH2:33][CH2:32][N:31]([C:25]3[CH:24]=[C:23]([O:22][CH3:21])[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=3)[CH2:36][CH2:35]2)=[S:20])[C:11]([O:18][CH3:19])=[N:12][C:13]=1[CH3:17]
Reactant: COc1cc(OC)cc(N2CCNCC2)c1
Reactant: COc1nc(C)c(C)cc1NC(=S)Oc1ccccc1
Product: COc1cc(OC)cc(N2CCN(C(=S)Nc3cc(C)c(C)nc3OC)CC2)c1
Yield: 69 %

Procedure:
Phenyl-N-(5,6-dimethyl-2-methoxypyridin-3-yl)thiocarbamate and 1-(3,5-dimethoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][NH2:8].C(O)(=O)C.[CH:13](=O)[C:14]([CH3:16])=[O:15].C([O-])(O)=O.[Na+]>O>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][N:8]=[CH:13][C:14](=[O:15])[CH3:16]
Reactant: NNc1ccccn1
Reactant: CC(=O)C=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: CC(=O)C=NNc1ccccn1
Temperature: 25 °C
Reaction time: 72 h
Yield: 40.9 %

Procedure:
To a solution of 2-pyridylhydrazine (10.0 g, 91.6 mmol) in water (30 mL) was added acetic acid (8.7 mL). This mixture was then added to a solution of pyruvaldehyde (16.5 g, 14.9 mL, 91.6 mmol) in water (400 mL). The mixture was stirred at room temperature for 3 days. The mixture was neutralized with NaHCO3 (solid) whereupon a yellow precipitate forms. The solid was isolated by filtration and then washed with water (30 mL). The solids were dried under high vacuum to afford 2-oxopropanal pyridin-2-ylhydrazone as a yellow solid (6.12 g, 41%).
Reaction SMILES: [C:1]1([C:7]2[O:8][C:9]3[CH:15]=[C:14](C=O)[CH:13]=[CH:12][C:10]=3[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:19]1C=CC=CC=1N>>[C:4]1([CH3:19])[CH:3]=[CH:2][C:1]([C:7]2[O:8][C:9]3[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=3[N:11]=2)=[CH:6][CH:5]=1
Reactant: Nc1ccccc1Cl
Reactant: O=Cc1ccc2nc(-c3ccccc3)oc2c1
Product: Cc1ccc(-c2nc3ccccc3o2)cc1

Procedure:
4.2 g (0.02 mole) of 2-(p-tolyl)-benzoxazole of the formula ##STR48## and 6.7 g (0.02 mole) of the Schiff's base, obtained from 2-phenyl-6-formyl-benzoxazole and o-chloroaniline, of the formula ##STR49## (melting point: 112.5°-113.5° C.) are dissolved in 80 ml of dimethyl formamide. To this solution are added in small amounts in the course of 20 minutes 2.1 g (0.002 mole) of sodium tert.butylate at 20° to 25° C. while introducing nitrogen. During the first 10 minutes, the reaction mixture is irradiated with ultraviolet light. While further introducing nitrogen and stirring for 2 hours at 20° to 25° C. the colour of the mixture changes gradually from yellow through violet brown to brown. Then 320 ml of methanol are added and the batch is cooled to 0° C. The precipitate is collected by filtration, washed repeatedly with a total of 40 ml of methanol and dried, affording 3.2 g (39% of theory) of 1-(2-phenyl-benzoxazol-6-yl)-2-(4'-benzoxazol-2-yl-phenyl)-ethylene of the formula ##STR50## in the form of a light beige-coloured powder with a melting point of 233°-237° C.
Reaction SMILES: [C@H:1]1([NH:10][C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[C:16]([NH2:21])[CH:17]=3)[N:12]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[CH3:22][N:23]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:24](Cl)=[O:25]>C(N(CC)CC)C>[C@H:1]1([NH:10][C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[C:16]([NH:21][C:24](=[O:25])[N:23]([CH3:22])[C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH:17]=3)[N:12]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1
Reactant: Nc1ccc2nc(N[C@@H]3CCc4ccccc43)ccc2c1
Reactant: CN(C(=O)Cl)c1ccccc1
Solvent: CCN(CC)CC
Product: CN(C(=O)Nc1ccc2nc(N[C@@H]3CCc4ccccc43)ccc2c1)c1ccccc1

Procedure:
The title compound, MS: m/e=409.7 (M+H+), was prepared in accordance with the general method 4 of example 16 from (R)—N2-indan-1-yl-quinoline-2,6-diamine, triethylamine and N-methyl-N-phenylcarbamoyl chloride.