Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6](=[O:23])[NH:7][C@H:8]1[CH2:13][C:12](=[O:14])[CH2:11][O:10][C@@H:9]1[C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1[F:22])([CH3:4])([CH3:3])[CH3:2].B(F)(F)F.[CH3:28]COCC.C[Si](C=[N+]=[N-])(C)C.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>C(Cl)Cl.C(OCC)C.C([O-])(O)=O.[Na+].CO>[C:1]([O:5][C:6](=[O:23])[NH:7][C@H:8]1[CH2:13][C:12](=[O:14])[CH2:11][CH2:28][O:10][C@@H:9]1[C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1[F:22])([CH3:2])([CH3:4])[CH3:3]
Reactant: CCOCC
Reactant: CC(C)(C)OC(=O)N[C@H]1CC(=O)CO[C@@H]1c1cc(F)ccc1F
Agent: C[Si](C)(C)C=[N+]=[N-]
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: FB(F)F
Solvent: CO
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N[C@H]1CC(=O)CCO[C@@H]1c1cc(F)ccc1F
Temperature: -78 °C
Reaction time: 0.17 h

Procedure:
To a solution of tert-butyl[(2R,3S)-5-oxo-2-(2,5-difluorophenyl)tetrahydro-2H-pyran-3-yl]carbamate (Intermediate 2 in U.S. Pat. No. 7,678,905, the contents of which are herein incorporated by reference in their entirety) (6 g, 18.3 mmol) in DCM (185 mL) cooled to −78° C. was added boron trifluoride diethyl etherate (9.3 mL, 73.3 mmol) dropwise via syringe. After stirring 10 min at −78° C., trimethylsilyldiazomethane (11 mL, 22 mmol, 2 M in hexane) was added dropwise via syringe and the reaction was stirred 1.5 h at −78° C. The reaction mixture was diluted with diethyl ether and sat. aqueous NaHCO3, extracted with diethyl ether (×2) and the combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The resulting oil was dissolved in a mixture of DCM (50 mL) and methanol (50 mL) and pyridiniump-toluenesulfonate (460 mg, 1.83 mmol) was added. The reaction was stirred 18 h at rt, then diluted with DCM and sat. aq. NaHCO3, washed with sat. aq. NaHCO3 and brine, then dried over Na2SO4, filtered and concentrated. The resulting oil was purified by column chromatography (100 g column, 8% to 70% EtOAc:Hex ramp) to provide the title compound as a white solid.
Reaction SMILES: [CH3:1][C:2]1([CH2:7][CH2:8][CH:9]=[C:10]([CH3:12])[CH3:11])[CH2:4][CH:3]1[CH2:5][NH2:6].[CH2:13]([O:15][C:16](Cl)=[O:17])[CH3:14].C(N(CC)CC)C>C(OCC)(=O)C>[CH3:1][C:2]1([CH2:7][CH2:8][CH:9]=[C:10]([CH3:12])[CH3:11])[CH2:4][CH:3]1[CH2:5][NH:6][C:16](=[O:17])[O:15][CH2:13][CH3:14]
Reactant: CC(C)=CCCC1(C)CC1CN
Reactant: CCOC(=O)Cl
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CCOC(=O)NCC1CC1(C)CCC=C(C)C
Temperature: 0 °C
Reaction time: 2 h
Yield: 66.8 %

Procedure:
1-[2-methyl-2-(4-methylpent-3-en-1-yl)cyclopropyl]methanamine (20.0 g, 0.12 mol) in 150 mL of ethyl acetate and ethylchloroformate (17.9 g, 0.165 mol) were charged to a reaction flask. The reaction mixture was then cooled to 0° C. Triethylamine (23.8 g, 0.165 mol) was slowly added while maintaining the reaction temperature at 0° C. Once the feed was complete the reaction mixture was aged for 2 hours than quenched with saturated sodium chloride solution. Kugelrohr distillation afforded 19.2 g of the product, 67% yield. 1H NMR (500 MHz, CDCl3) S: 0.07-0.12 (m, 1H), 0.44-0.49 (m, 1H), 0.75-0.79 (m, 1H), 1.04-1.06 (2s, 3H), 1.24 (t, J=6.89 Hz, 3H), 1.24-1.42 (m, 1H), 1.29-1.42 (m, 1H), 1.61 (s, 3H), 1.69 (s, 3H), 2.04-2.08 (m, 2H), 2.99-3.35 (m, 2H), 4.11 (q, J=6.82 Hz, 2H), 4.62 (br. s, 1H), 5.07-5.13 (m, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:56]=[CH:55][CH:54]=[CH:53][C:4]=1[CH2:5][O:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH:18]2[O:30][CH2:31][CH2:32][O:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[CH2:40][CH2:41]OS(C2C=CC(C)=CC=2)(=O)=O)=[CH:13][CH:12]=1.[O:57]1[CH2:61][CH2:60][NH:59][C:58]1=[O:62]>>[CH3:1][O:2][C:3]1[CH:56]=[CH:55][CH:54]=[CH:53][C:4]=1[CH2:5][O:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[CH:13][C:14]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:27])[CH3:28])=[O:24])[CH2:19][CH:18]2[O:30][CH2:31][CH2:32][O:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[CH2:40][CH2:41][N:59]2[CH2:60][CH2:61][O:57][C:58]2=[O:62])=[CH:15][CH:16]=1
Reactant: O=C1NCCO1
Reactant: COc1ccccc1COCCCOc1ccc(C2CCN(C(=O)OC(C)(C)C)CC2OCCOc2ccccc2CCOS(=O)(=O)c2ccc(C)cc2)cc1
Product: COc1ccccc1COCCCOc1ccc(C2CCN(C(=O)OC(C)(C)C)CC2OCCOc2ccccc2CCN2CCOC2=O)cc1

Procedure:
Analogously to Example 27a, 020 g of tert-butyl 4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}-3-(2-{2-[2-(toluene-4-sulphonyloxy)ethyl]phenoxy}ethoxy)piperidine-1-carboxylate (Example 26b) and 0.44 g of oxazolidin-2-one are reacted. The title compound is obtained as a colourless oil. Rf=0.27 (2:1 EtOAc-heptane).
Reaction SMILES: C[O:2][C:3](=O)[C:4]1[CH:9]=[C:8]([NH2:10])[CH:7]=[CH:6][C:5]=1[O:11][C:12]([F:15])([F:14])[F:13].[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[NH2:10][C:8]1[CH:7]=[CH:6][C:5]([O:11][C:12]([F:13])([F:14])[F:15])=[C:4]([CH2:3][OH:2])[CH:9]=1
Reactant: COC(=O)c1cc(N)ccc1OC(F)(F)F
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: Nc1ccc(OC(F)(F)F)c(CO)c1
Reaction time: 1 h
Yield: 93.2 %

Procedure:
5-Amino-2-trifluoromethoxybenzoic acid methyl ester (3.0 g, 12.8 mmol) was dissolved under nitrogen in THF (20 mL) in a three-necked flask equipped with a thermometer and a separatory funnel. With stirring and ice-cooling lithium aluminium hydride (1 M in THF, 15 mL) was added dropwise over 10 min. Stirring was continued at room temperature for 1 hour, and the reaction mixture was concentrated in vacuo. The residue was suspended in DCM (150 mL) and water (50 mL), and filtered through celite. The filtrate was partitioned between DCM and water. The combined organic phases were washed with water (2×20 mL), dried (magnesium sulphate) and concentrated in vacuo to give 2.47 g of (5-amino-2-trifluoromethoxy-phenyl)methanol
Reaction SMILES: [NH2:1]/[C:2](/[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[CH:3]\[C:4]#[N:5].[SH2:12]>CCO.C1COCC1>[C:6]1([C:2]2[CH:3]=[C:4]([NH2:5])[S:12][N:1]=2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: N#C/C=C(\N)c1ccccc1
Reactant: S
Solvent: CCO
Solvent: C1CCOC1
Product: Nc1cc(-c2ccccc2)ns1
Reaction time: 20 h

Procedure:
To a solution of (Z)-3-amino-3-phenylacrylonitrile (95 mg, 0.660 mmol) in EtOH (1.0 mL) and THF (1.0 mL) in a sealed tube, H2S gas was bubbled through for 5 min. It was then stirred at 90 C for 20 h. The mixture was concentrated in vacuo. The residue was dissolved in MeOH (2.0 mL), aq. H2O2 (30%, 0.5 mL) was added. After being stirred at room temperature for 2 min, the reaction was completed. The mixture was concentrated in vacuo. The residue was purified by HPLC to give 3-phenylisothiazol-5-amine (22 mg).
Reaction SMILES: [Si]([O:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:18]=1[N:17]=[C:16]([C:19]1[N:23]3[CH:24]=[CH:25][C:26]([CH3:28])=[CH:27][C:22]3=[N:21][N:20]=1)[CH:15]=[CH:14]2)(C(C)(C)C)(C)C.O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.[NH4+].[Cl-].CCOC(C)=O.O>[CH3:28][C:26]1[CH:25]=[CH:24][N:23]2[C:19]([C:16]3[CH:15]=[CH:14][C:13]4[C:18](=[C:9]([OH:8])[CH:10]=[CH:11][CH:12]=4)[N:17]=3)=[N:20][N:21]=[C:22]2[CH:27]=1
Reactant: Cc1ccn2c(-c3ccc4cccc(O[Si](C)(C)C(C)(C)C)c4n3)nnc2c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1CCOC1
Product: Cc1ccn2c(-c3ccc4cccc(O)c4n3)nnc2c1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 77.7 %

Procedure:
8-(tert-butyldimethylsilyloxy)-2-(7-methyl-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinoline (0.580 g, 1.49 mmol) was suspended in THF (2 mL) and the solution was cooled to 0° C. Tetrabutylammonium fluoride hydrate (0.582 g, 2.23 mmol) was added to the solution and the mixture stirred at 0° C. for 10 minutes, then warmed to ambient temperature and stirred for 4 hours. The mixture was diluted with a saturated aqueous NH4Cl solution and EtOAc. The resulting white solid was isolated by vacuum filtration and was combined with the organic layer which was concentrated. The solid thus obtained was slurried in H2O for 10 minutes and the solids isolated by vacuum filtration and dried to provide the title compound (0.320 g, 78%) as a white solid. MS ESI (+) m/z 277.1 (M+1) detected.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[N:19]=[CH:18][C:17]4[N:16]([C:20]5[CH:28]=[CH:27][CH:26]=[C:25]6[C:21]=5[CH:22]=[CH:23][N:24]6C(OC(C)(C)C)=O)[CH2:15][C@@H:14]5[CH2:36][O:37][CH2:38][CH2:39][N:13]5[C:12]=4[N:11]=3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[F:40][C:41]([F:46])([F:45])[C:42]([OH:44])=[O:43]>C(Cl)Cl>[C:42]([OH:44])([C:41]([F:46])([F:45])[F:40])=[O:43].[NH:1]1[C:9]2[C:4](=[C:5]([C:10]3[N:19]=[CH:18][C:17]4[N:16]([C:20]5[CH:28]=[CH:27][CH:26]=[C:25]6[C:21]=5[CH:22]=[CH:23][NH:24]6)[CH2:15][C@@H:14]5[CH2:36][O:37][CH2:38][CH2:39][N:13]5[C:12]=4[N:11]=3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1
Reactant: CC(C)(C)OC(=O)n1ccc2c(N3C[C@@H]4COCCN4c4nc(-c5cccc6[nH]ccc56)ncc43)cccc21
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: c1cc(-c2ncc3c(n2)N2CCOC[C@H]2CN3c2cccc3[nH]ccc23)c2cc[nH]c2c1
Yield: 28 %

Procedure:
(R)-tert-Butyl 4-(2-(1H-indol-4-yl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)-1H-indole-1-carboxylate (PREPARATION x65, 9 mg, 0.017 mmol) was dissolved in CH2Cl2 (1 mL) and trifluoroacetic acid (1 mL) and the mixture was stirred at room temperature for 30 minutes. The material was then concentrated in vacuo and the product was purified by LC/MS using a 20-45% CH3CN gradient in H2O (with 0.035% TFA). The pure fractions were combined and lyophilized to afford a TFA salt of the title compound as a yellow solid (2 mg, 28%). 1H NMR (400 MHz, CD3CN) δ ppm 3.36-3.61 (m, 3H), 3.68-3.87 (m, 2H), 3.97-4.07 (m, 1H), 4.07-4.20 (m, 2H), 4.91-5.00 (m, 1H), 6.28-6.38 (m, 1H), 6.98-7.09 (m, 2H), 7.12-7.17 (m, 1H), 7.22-7.35 (m, 3H), 7.44-7.51 (m, 2H), 7.65-7.75 (m, 2H), 9.57-9.67 (m, 1H), 9.67-9.81 (m, 1H); ESI-MS m/z [M+H]+ calc'd for C25H22N6O, 423.19. found 423.3.
Reaction SMILES: Br[CH:2]=[C:3]1[C:9]2[CH:10]=[CH:11][C:12]([F:14])=[CH:13][C:8]=2[CH2:7][O:6][C:5]2[CH:15]=[C:16]([F:19])[CH:17]=[CH:18][C:4]1=2.CC1(C)C(C)(C)OB([C:28]2[CH:37]=[CH:36][C:31]3[NH:32][C:33](=[O:35])[NH:34][C:30]=3[CH:29]=2)O1.C([O-])([O-])=O.[Na+].[Na+].O1CCOCC1>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.CO>[F:19][C:16]1[CH:17]=[CH:18][C:4]2[C:3](=[CH:2][C:28]3[CH:37]=[CH:36][C:31]4[NH:32][C:33](=[O:35])[NH:34][C:30]=4[CH:29]=3)[C:9]3[CH:10]=[CH:11][C:12]([F:14])=[CH:13][C:8]=3[CH2:7][O:6][C:5]=2[CH:15]=1
Reactant: Fc1ccc2c(c1)COc1cc(F)ccc1C2=CBr
Reactant: CC1(C)OB(c2ccc3[nH]c(=O)[nH]c3c2)OC1(C)C
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: [Na+]
Solvent: C1COCCO1
Solvent: CO
Product: O=c1[nH]c2ccc(C=C3c4ccc(F)cc4COc4cc(F)ccc43)cc2[nH]1
Temperature: -26 °C
Yield: 27.1 %

Procedure:
Following procedures essentially as described in Example 219, mix 11-bromomethylene-3,8-difluoro-6,11-dihydro-dibenzo[b,e]oxepine (E-isomer, 326 mg, 1.0 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,3-dihydro-benzoimidazol-2-one (250 mg, 0.961 mmol), Na2CO3 (2M in water, 1.20 mL, 2.40 mmol), dioxane (7 mL), and Pd(PPh3)4 (58 mg, 0.051 mmol). Purify the crude product on silica gel (12 g) eluting with 50% to 70% THF/hexanes to afford two lots of yellow solid weighing 180 mg and 151 mg. Dissolve the 180 mg lot in boiling MeOH (20 mL), concentrate to 10 mL and cool to −26° C. to precipitate 165 mg (46%) of the title compound as a white solid. Repeat the recrystallization on the 151 mg lot to afford 98 mg (27%) of the title compound as a white solid. HPLC (ISO80-10) t=2.38 min, 97%; MS [ES] 375 (M−H), 377 (M+H); 1H-NMR (DMSO-d6) δ 10.57 (s, 1H), 10.46 (s, 1H), 7.57 (dd, 1H, J=8.4, 7.0 Hz), 7.49 (dd, 1H, J=9.2, 2.6 Hz), 7.08 (td, 1H, J=12.5, 4.3 Hz), 7.01 (d, 1H, J=5.7 Hz), 6.97 (s, 1H), 6.79 (td, 1H, J=12.0, 4.2 Hz), 6.73 (d, 1H, J=8.4 Hz), 6.67 (d, 1H, J=8.4 Hz), 6.61 (dd, 1H, J=10.6, 2.6 Hz), 6.52 (s, 1H), 5.78-4.78 (br d, 2H).
Reaction SMILES: [CH3:1][S:2][C:3](=[NH:14])[NH:4][N:5]=[C:6](OCC)[CH2:7][CH2:8][CH2:9][CH3:10].[C:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[C:23]1[CH:28]=[CH:27][C:26]([CH2:29][NH2:30])=[CH:25][CH:24]=1)#[N:16]>CCO>[CH3:1][S:2][C:3](=[NH:14])[NH:4][N:5]=[C:6]([NH:30][CH2:29][C:26]1[CH:25]=[CH:24][C:23]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[C:15]#[N:16])=[CH:28][CH:27]=1)[CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: CCCCC(=NNC(=N)SC)OCC
Reactant: N#Cc1ccccc1-c1ccc(CN)cc1
Solvent: CCO
Product: CCCCC(=NNC(=N)SC)NCc1ccc(-c2ccccc2C#N)cc1
Temperature: 25 °C
Reaction time: 144 h
Yield: 71.4 %

Procedure:
A mixture of 5.50 g (25.3 mmol) of ethyl valerate S-methylisothiosemicarbazone (from Step B), 6.55 g (31.5 mmol) of [(2'-cyanobiphenyl-4-yl)methyl]amine (EP 0412594 published Feb. 13, 1991, Merck Case No. 17959IA), and 57 ml of dry EtOH was stirred under N2 at room temperature for 6 days and then concentrated in vacuo at ≤30° C. The residue was chromatographed on a column of silica gel (38×8.8 cm) packed in CH2Cl2. Gradient elution with 0.5-2% MeOH in CH2Cl2 and concentration of combined product fractions gave 6.86 g (71%) of the title compound as a yellow gum; satisfactory purity by TLC in 19:1 CH2Cl2 -MeOH. NMR indicated a mixture of syn and anti isomers.
Reaction SMILES: I[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].[CH:12]12[CH2:17][CH:16]1[C:15](=[O:18])[NH:14][C:13]2=[O:19].C(=O)([O-])[O-].[K+].[K+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.ClCCl>[CH2:2]([N:14]1[C:15](=[O:18])[CH:16]2[CH:12]([CH2:17]2)[C:13]1=[O:19])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11]
Reactant: CCCCCCCCCCI
Reactant: O=C1NC(=O)C2CC12
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])[O-]
Agent: [Br-]
Solvent: ClCCl
Product: CCCCCCCCCCN1C(=O)C2CC2C1=O
Reaction time: 24 h

Procedure:
1-Iododecane (1.21 g) was added to a stirred mixture of 3-azabicyclo[3.1.0]hexane-2,4 dione (0.5 g), potassium carbonate (0.62 g) and tetrabutylammonium bromide (1.45 g) in dichloromethane (50 ml) at room temperature and the resulting mixture was stirred for 24 hours. The mixture was filtered and the filtrate was then washed with water (2×100 ml), dried (MgSO4) and evaporated in vacuo to give a brown oil. The oil was purified by column chromatography on silica gel (100 g) using hexane as eluant. Combination and evaporation of the appropriate fractions gave the title compound as a colourless oil.
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]([CH3:13])[CH3:12])=[C:4](Cl)[N:3]=1.[I:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][CH:23]=1)[CH2:19][NH2:20]>C(N(CC)CC)C>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]([CH3:13])[CH3:12])=[C:4]([NH:20][CH2:19][C:18]2[CH:21]=[CH:22][CH:23]=[C:16]([I:15])[CH:17]=2)[N:3]=1
Reactant: NCc1cccc(I)c1
Reactant: CC(C)n1cnc2c(Cl)nc(Cl)nc21
Solvent: CCN(CC)CC
Product: CC(C)n1cnc2c(NCc3cccc(I)c3)nc(Cl)nc21

Procedure:
2-Chloro-6-[(3-iodobenzyl)amino]-9-(2-propyl)purine is prepared from 2,6-dichloro-9-(2-propyl)purine (see Example 15 for preparation), 3-iodobenzylamine, and triethylamine essentially as described above in Example 1, Scheme A, step b.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[C:5]([N:7]2[C:19]3[C:18]4[CH:17]=[C:16]([C:20]5[CH:21]=[N:22][C:23]([O:29][CH3:30])=[C:24]([N+:26]([O-])=O)[CH:25]=5)[CH:15]=[CH:14][C:13]=4[N:12]=[CH:11][C:10]=3[N:9]([CH3:31])[C:8]2=[O:32])[C:4]([CH3:33])=[N:3]1.[H][H]>C1COCC1.CO.[Pd]>[NH2:26][C:24]1[CH:25]=[C:20]([C:16]2[CH:15]=[CH:14][C:13]3[N:12]=[CH:11][C:10]4[N:9]([CH3:31])[C:8](=[O:32])[N:7]([C:5]5[C:4]([CH3:33])=[N:3][N:2]([CH3:1])[CH:6]=5)[C:19]=4[C:18]=3[CH:17]=2)[CH:21]=[N:22][C:23]=1[O:29][CH3:30]
Reactant: [H][H]
Reactant: COc1ncc(-c2ccc3ncc4c(c3c2)n(-c2cn(C)nc2C)c(=O)n4C)cc1[N+](=O)[O-]
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CO
Product: COc1ncc(-c2ccc3ncc4c(c3c2)n(-c2cn(C)nc2C)c(=O)n4C)cc1N

Procedure:
A solution of 1-(1,3-dimethyl-1H-pyrazol-4-yl)-8-(6-methoxy-5-nitro-pyridin-3-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one (Example 66, 50 mg, 0.112 mmol) in 5 ml THF and 5 ml MeOH was stirred in presence of palladium 10% on charcoal under 1.1 bar of hydrogen for 5 h at rt. The reaction mixture was filtered over Celite and the catalyst was washed with MeOH/THF. The filtrate was evaporated and the crude product was purified by Prep.HPLC (H2O (0.1% TFA)/CH3CN 95:5 to 50:50). The fractions containing products were collected together, basified with NaHCO3, concentrated and extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and evaporated to give the title compound as a light yellow solid. (HPLC: tR 2.29 min (Method A); M+H=416 MS-ES; 1H-NMR (d6-DMSO, 400 MHz) 8.94 (s, 1H), 8.12-8.10 (m, 1H), 8.08-8.05 (m, 1H), 7.76-7.72 (m, 1H), 7.47-7.45 (m, 1H), 7.43-7.41 (m, 1H), 7.00-6.97 (m, 11-1), 5.11 (s, br, 2H), 3.92 (s, 3H), 3.89 (s, 3H), 3.57 (s, 3H), 1.94 (s, 3H))
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1.F[C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][C:17]=1[N+:23]([O-:25])=[O:24].O>CN(C=O)C>[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:16]2[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][C:17]=2[N+:23]([O-:25])=[O:24])=[CH:10][CH:9]=1
Reactant: Oc1ccc(Cl)cc1
Reactant: Nc1ccc(F)c([N+](=O)[O-])c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Nc1ccc(Oc2ccc(Cl)cc2)c([N+](=O)[O-])c1
Reaction time: 0.5 h

Procedure:
1.4 g of potassium carbonate were added to a solution of 1.29 g of 4-chlorophenol in 8 ml of DMF and, after stirring for 30 minutes, 1.6 g of 4-fluoro-3-nitroaniline were added, and the mixture was stirred at 100° C. for 3 hours. After cooling, 80 ml of water were added and, after brief stirring, the precipitate was filtered off with suction and dried in vacuo at 40° C.
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[CH:14]=[CH:13][C:9]3[O:10][CH2:11][O:12][C:8]=3[C:7]=2[C:15]2[C:16]3[NH:23][CH:22]=[C:21]([C:24]([OH:26])=O)[C:17]=3[N:18]=[CH:19][N:20]=2)[CH2:3][CH2:2]1.[C:27]([O:31][C:32]([N:34]1[CH2:38][CH2:37][CH:36]([CH2:39][NH2:40])[CH2:35]1)=[O:33])([CH3:30])([CH3:29])[CH3:28]>>[C:27]([O:31][C:32]([N:34]1[CH2:38][CH2:37][CH:36]([CH2:39][NH:40][C:24]([C:21]2[C:17]3[N:18]=[CH:19][N:20]=[C:15]([C:7]4[C:8]5[O:12][CH2:11][O:10][C:9]=5[CH:13]=[CH:14][C:6]=4[O:5][CH2:4][CH:1]4[CH2:3][CH2:2]4)[C:16]=3[NH:23][CH:22]=2)=[O:26])[CH2:35]1)=[O:33])([CH3:30])([CH3:29])[CH3:28]
Reactant: CC(C)(C)OC(=O)N1CCC(CN)C1
Reactant: O=C(O)c1c[nH]c2c(-c3c(OCC4CC4)ccc4c3OCO4)ncnc12
Product: CC(C)(C)OC(=O)N1CCC(CNC(=O)c2c[nH]c3c(-c4c(OCC5CC5)ccc5c4OCO5)ncnc23)C1

Procedure:
Starting from 4-(5-cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid (example A67) and 3-aminomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester the title compound is obtained as colorless solid.
Reaction SMILES: [OH:1][C:2]1[CH:6]=[C:5]([CH2:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[N:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:3]=1.Cl[CH2:21][C:22]1[CH:41]=[CH:40][C:25]([O:26][CH2:27][C:28]2[N:29]=[C:30]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[O:31][C:32]=2[CH3:33])=[CH:24][CH:23]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH3:33][C:32]1[O:31][C:30]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)=[N:29][C:28]=1[CH2:27][O:26][C:25]1[CH:24]=[CH:23][C:22]([CH2:21][O:1][C:2]2[CH:6]=[C:5]([CH2:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[N:4]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:3]=2)=[CH:41][CH:40]=1
Reactant: Cc1oc(-c2ccccc2)nc1COc1ccc(CCl)cc1
Reactant: CCOC(=O)CCc1cc(O)nn1-c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)CCc1cc(OCc2ccc(OCc3nc(-c4ccccc4)oc3C)cc2)nn1-c1ccccc1
Temperature: 60 °C
Reaction time: 4 h
Yield: 95.3 %

Procedure:
A mixture of ethyl 3-(3-hydroxy-1-phenyl-1H-pyrazol-5-yl)propionate (500 mg), 4-(4-chloromethylphenoxymethyl)-5-methyl-2-phenyloxazole (600 mg), potassium carbonate (530 mg) and N,N-dimethylformamide (10 ml) was stirred at 60° C. for 4 hrs. The reaction mixture was poured into water and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and ethyl 3-[3-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyloxy]-1-phenyl-1H-pyrazol-5-yl]propionate (980 mg, yield 95%) was obtained as a colorless oil from a fraction eluted with ethyl acetate-hexane (1:1, volume ratio).
Reaction SMILES: [CH3:1][C:2]1([CH3:37])[C:11]2[C:6](=[CH:7][C:8]([NH:12][C:13]([N:15]3[CH2:20][CH2:19][N:18]([C:21]4[C:26]([C:27]([F:30])([F:29])[F:28])=[CH:25][CH:24]=[CH:23][N:22]=4)[CH2:17][CH2:16]3)=[O:14])=[CH:9][CH:10]=2)[CH:5](C(=O)C(F)(F)F)[NH:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+]>CO.O>[CH3:1][C:2]1([CH3:37])[C:11]2[C:6](=[CH:7][C:8]([NH:12][C:13]([N:15]3[CH2:20][CH2:19][N:18]([C:21]4[C:26]([C:27]([F:29])([F:28])[F:30])=[CH:25][CH:24]=[CH:23][N:22]=4)[CH2:17][CH2:16]3)=[O:14])=[CH:9][CH:10]=2)[CH2:5][NH:4][CH2:3]1
Reactant: CC1(C)CNC(C(=O)C(F)(F)F)c2cc(NC(=O)N3CCN(c4ncccc4C(F)(F)F)CC3)ccc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CO
Product: CC1(C)CNCc2cc(NC(=O)N3CCN(c4ncccc4C(F)(F)F)CC3)ccc21
Temperature: 50 °C

Procedure:
A suspension of N-(4,4-dimethyl-1-trifluoroacetyl-1,2,3,4-tetrahydroisoquinol-7-yl)-4-(3-trifluoromethyl-2-pyridyl)-piperazine-1-carboxamide (30 mg, 0.057 mmol) and potassium carbonate (48 mg, 0.348 mmol) in methanol (4 ml) and water (4 ml) was heated at 50° C. for 6 h. After this period, the solvents were evaporated in vacuo and the residue partitioned between DCM (30 ml) and water (30 ml). The aqueous layer was re-extracted with DCM (2×30 ml) and then the combined organic layers dried (Na2SO4) and the solvents evaporated in vacuo to give the title compound as a white solid. 1H NMR (400 MHz, DMSO) δ (ppm): 8.45 (dd, 1H), 7.89 (dd, 1H), 7.22 (d, 1H), 7.10 (dd, 1H), 7.00-7.05 (m, 2H), 6.55 (s, 1H), 3.95 (s, 2H), 3.60-3.65 (m, 4H), 3.30-3.32 (m, 4H), 2.82 (s, 2H), 2.00 (br-s, 1H), 1.23 (s, 6H). MS (ES): MH+ 434.
Reaction SMILES: [SH:1][CH2:2][CH:3]1[CH2:7][O:6][C:5]([CH2:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])([CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[S:4]1.[CH2:22]([C:25]1[C:35]([OH:36])=[C:34]([C:37](=[O:39])[CH3:38])[CH:33]=[CH:32][C:26]=1[O:27][CH2:28][CH:29]1[O:31][CH2:30]1)[CH2:23][CH3:24].C(=O)([O-])[O-].[K+].[K+]>>[C:37]([C:34]1[CH:33]=[CH:32][C:26]([O:27][CH2:28][CH:29]([OH:31])[CH2:30][S:1][CH2:2][CH:3]2[CH2:7][O:6][C:5]([CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])([CH2:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[S:4]2)=[C:25]([CH2:22][CH2:23][CH3:24])[C:35]=1[OH:36])(=[O:39])[CH3:38]
Reactant: CCOC(=O)CCC1(CCC(=O)OCC)OCC(CS)S1
Reactant: CCCc1c(OCC2CO2)ccc(C(C)=O)c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CCCc1c(OCC(O)CSCC2COC(CCC(=O)OCC)(CCC(=O)OCC)S2)ccc(C(C)=O)c1O

Procedure:
The title compound was prepared according to the procedure of Example 2 using the mercaptan produced in Example 1 (2.0 g, 0.0066 mol), 3-(2-n-propyl-3-hydroxy-4-acetylphenoxy)-1,2-epoxypropane (described in U.S. Pat. No. 4,565,882) (1.5 g, 0.006 mol) and anhydrous potassium carbonate (3.0 g). The crude product was chromatographed on silica gel using 40% ethyl acetate/hexane as eluent to give 3.22 g (92%) of the product as an oil.