Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:21])([F:20])[C:3]1[CH:4]=[C:5]([C:9]2[CH:18]=[CH:17][C:16]3[C:11](=[C:12]([NH2:19])[CH:13]=[CH:14][CH:15]=3)[N:10]=2)[CH:6]=[CH:7][CH:8]=1.CCN(C(C)C)C(C)C.[N:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[S:37](Cl)(=[O:39])=[O:38].C([O-])(O)=O.[Na+]>C(Cl)Cl>[F:21][C:2]([F:1])([F:20])[C:3]1[CH:4]=[C:5]([C:9]2[CH:18]=[CH:17][C:16]3[C:11](=[C:12]([NH:19][S:37]([C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][N:31]=4)(=[O:39])=[O:38])[CH:13]=[CH:14][CH:15]=3)[N:10]=2)[CH:6]=[CH:7][CH:8]=1
Reactant: Nc1cccc2ccc(-c3cccc(C(F)(F)F)c3)nc12
Reactant: O=S(=O)(Cl)c1ccccn1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: O=S(=O)(Nc1cccc2ccc(-c3cccc(C(F)(F)F)c3)nc12)c1ccccn1
Temperature: 25 °C
Reaction time: 18 h
Yield: 16.8 %

Procedure:
To a solution of 2-(3-(trifluoromethyl)phenyl)quinolin-8-amine (0.10 g, 0.347 mmol) in CH2Cl2 (10 mL) was added DIPEA (0.120 mL, 0.695 mmol) followed by pyridine-2-sulfonyl chloride (0.065 g, 0.366 mmol). The mixture was stirred at room temperature for 18 hours. An aqueous solution of saturated NaHCO3 was added (30 mL), the resulting precipitate was collected by filtration and washed with methanol to obtain N-(2-(3-(trifluoromethyl)phenyl)quinolin-8-yl)pyridine-2-sulfonamide (0.025 g, 17% yield).
Reaction SMILES: [CH2:1]([O:3][C:4]([NH:6][C:7]1[S:11][N:10]=[N:9][C:8]=1[C:12]([O:14]CC)=[O:13])=[O:5])[CH3:2].Cl>C(O)C>[CH2:1]([O:3][C:4]([NH:6][C:7]1[S:11][N:10]=[N:9][C:8]=1[C:12]([OH:14])=[O:13])=[O:5])[CH3:2]
Reactant: CCOC(=O)Nc1snnc1C(=O)OCC
Agent: Cl
Solvent: CCO
Product: CCOC(=O)Nc1snnc1C(=O)O

Procedure:
A suspension of sodium thiocyanate (24.30 g, 0.30 mole) in acetonitrile (120 ml), maintained at 19° C., was treated dropwise over 22 minutes with a solution of ethyl chloroformate (28.7 ml, 0.30 mole) in acetonitrile (25 ml). The resultant mixture was stirred for 25 minutes at 20° C. and then ethyl diazoacetate (31.5 ml, 0.30 mole) was added. After stirring for 24 hours, 6.0 N hydrochloric acid (300 ml) was added with cooling Acetonitrile solvent was removed in vacuo and the residual aqueous suspension was extracted several times with ether. Combined ether extracts were washed with water, dried (Na2SO4) and evaporated to leave 51.0 g of ethyl 5-ethoxycarbonylamino-1,2,3-thiadiazole-4-carboxylate. This ester was hydrolyzed by refluxing for 6 hours in a mixture of ethanol (80 ml) and aqueous 6 N hydrochloric acid (400 ml) to yield the title acid; m.p. 179°-180° dec. after crystallization from nitromethane.
Reaction SMILES: C1C=C(Cl)C=C(C(OO)=[O:9])C=1.[Br:12][C:13]1[C:14]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[N:15][C:16]([NH:19][C:20]2[O:21][C@:22]3([CH2:30][N:31]=2)[CH:27]2[CH2:28][CH2:29][N:24]([CH2:25][CH2:26]2)[CH2:23]3)=[N:17][CH:18]=1>C1COCC1>[Br:12][C:13]1[C:14]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[N:15][C:16]([NH:19][C:20]2[O:21][C@:22]3([CH2:30][N:31]=2)[CH:27]2[CH2:28][CH2:29][N+:24]([O-:9])([CH2:25][CH2:26]2)[CH2:23]3)=[N:17][CH:18]=1
Reactant: Brc1cnc(NC2=NC[C@@]3(CN4CCC3CC4)O2)nc1-c1ccccc1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: C1CCOC1
Product: [O-][N+]12CCC(CC1)[C@]1(CN=C(Nc3ncc(Br)c(-c4ccccc4)n3)O1)C2
Temperature: 25 °C
Reaction time: 18 h
Yield: 61.8 %

Procedure:
mCPBA (0.060 g, 0.266 mmol) was added to a suspension of (R)—N-(5-bromo-4-phenylpyrimidin-2-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (0.1 g, 0.241 mmol) in THF (10 ml). The mixture was stirred at room temperature for 18 h, concentrated, and purified by silica gel chromatography (5-25% 9:1 methanol:ammonium hydroxide-ethyl acetate) to afford (S)-2-(5-bromo-4-phenylpyrimidin-2-ylamino)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octane]1′-oxide as an off-white solid (0.066 g, 0.149 mmol, 62%). 1H NMR (400 MHz, MeOD) δ ppm 8.72 (1H, s), 7.74 (2H, dd, J=6.92, 2.64 Hz), 7.39-7.53 (3H, m), 4.01 (1H, d, J=10.58 Hz), 3.85 (1H, d, J=10.32 Hz), 3.61-3.74 (2H, m), 3.37-3.50 (3H, m), 3.19-3.26 (1H, m), 2.37-2.51 (1H, m), 2.26-2.33 (1H, m), 1.95-2.20 (3H, m). LC/MS RT=1.78; [M+2]+=432.19.
Reaction SMILES: [NH2:1][CH:2]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=1)[CH:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[F:11])[OH:4].[C:23]1([CH2:29][CH2:30][C:31](Cl)=[O:32])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(=O)([O-])O.[Na+]>C(OCC)(=O)C.O>[F:11][C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=1[CH:3]([OH:4])[CH:2]([NH:1][C:31](=[O:32])[CH2:30][CH2:29][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:20])[F:21])=[CH:15][CH:14]=1
Reactant: O=C(Cl)CCc1ccccc1
Reactant: NC(Cc1ccc(C(F)(F)F)cc1)C(O)c1ccccc1F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Product: O=C(CCc1ccccc1)NC(Cc1ccc(C(F)(F)F)cc1)C(O)c1ccccc1F
Temperature: 25 °C
Reaction time: 8 h
Yield: 77.5 %

Procedure:
To a solution of (1RS,2SR)-2-amino-1-(2-fluorophenyl)-3-(4-(trifluoromethyl)phenyl)-1-propanol (450 mg, 1.44 mmol) in ethyl acetate (20 ml) were added 3-phenylpropionyl chloride (320 ml, 2.15 mmol) and saturated aqueous sodium hydrogen carbonate (20 ml) and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (100 ml) and extracted with ethyl acetate (100 ml×2). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was recrystallized from ethyl acetate-hexane to give the title compound (497 mg, 78%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:25]=[CH:24][CH:23]=[CH:22][C:11]=3[C:12]=2[C:13](=[O:21])[C:14]2[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=2)=[CH:4][CH:3]=1.[CH2:26]([N:28]([CH2:33][CH3:34])[CH2:29][CH2:30][CH2:31]Cl)[CH3:27]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:25]=[CH:24][CH:23]=[CH:22][C:11]=3[C:12]=2[C:13](=[O:21])[C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:31][CH2:30][CH2:29][N:28]([CH2:33][CH3:34])[CH2:26][CH3:27])=[CH:16][CH:15]=2)=[CH:4][CH:3]=1
Reactant: CCN(CC)CCCCl
Reactant: O=C(c1ccc(O)cc1)c1c(-c2ccc(Cl)cc2)oc2ccccc12
Product: CCN(CC)CCCOc1ccc(C(=O)c2c(-c3ccc(Cl)cc3)oc3ccccc23)cc1

Procedure:
Reaction of 2-(4-chlorophenyl)-3-(4-hydroxybenzoyl)-benzofuran with 3-diethylaminopropyl chloride according to the procedure of Example 1 gives the title compound.
Reaction SMILES: [H-].[Na+].[CH3:3][N:4]([CH3:16])[C:5]1[CH:15]=[CH:14][C:8]([C:9]([O:11]CC)=O)=[CH:7][CH:6]=1.[CH3:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20].Cl>O1CCCC1>[CH3:16][N:4]([CH3:3])[C:5]1[CH:6]=[CH:7][C:8]([C:9](=[O:11])[CH2:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:14][CH:15]=1
Reactant: CCOC(=O)c1ccc(N(C)C)cc1
Reactant: CC(=O)C(C)(C)C
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CN(C)c1ccc(C(=O)CC(=O)C(C)(C)C)cc1
Reaction time: 3 h
Yield: 70 %

Procedure:
Into a 100 ml three-necked flask equipped with a stirrer, a dropping funnel, a reflux condenser, and a nitogen-inlet tube, were charged 2.08 gm (31 mmol) of 60% sodium hydride and 5.0 gm (26 mmol) of ethyl 4-dimethylaminobenzoate. The mixture was dispersed in 40 ml of tetrahydrofuran and heated under refluxing. To the mixture was dropwise added 3.0 gm (30 mmol) of pinacolone and the mixture was heated with stirring for 3 hours. After cooling, 50 ml of 1N hydrochloric acid was added to the reaction mixture, and the organic layer was extracted twice with chloroform. The extract was thoroughly washed with water and dried over anhydrous magnesium sulfate. The solvent was removed by evaporation to obtain an yellow oil. The oily substance was submitted to the Kugelrohr distillation 150° C., 1 mmHg, and crystallized from hexane to give 4.5 gm (yield: 70%) of yellow solid product.
Reaction SMILES: [H-].[Na+].C([O:5][CH2:6][CH3:7])=O.[CH3:8][C:9]1(C)[CH2:25][C:13]2=[C:14]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=3)[S:15][C:16]([S:17][CH3:18])=[C:12]2[C:11](=[O:26])[CH2:10]1.CO>C1COCC1>[CH3:8][C:9]1([CH3:10])[CH2:25][C:13]2=[C:14]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=3)[S:15][C:16]([S:17][CH3:18])=[C:12]2[C:11](=[O:26])[C:7]1=[CH:6][OH:5]
Reactant: CSc1sc(-c2ccccn2)c2c1C(=O)CC(C)(C)C2
Reactant: CCOC=O
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: CSc1sc(-c2ccccn2)c2c1C(=O)C(=CO)C(C)(C)C2
Temperature: 25 °C
Reaction time: 2 h
Yield: 39.9 %

Procedure:
To a solution of sodium hydride (108 mg of a 60% dispersion in mineral oil, 2.7 mmol) and ethyl formate (0.55 mL, 6.8 mmol) at 0C in THF (5 mL) was added a solution of 6,6-dimethyl-3-methylthio-1-(pyrid-2-yl)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one (205 mg, 0.68 mmol) in THF (5 mL). The mixture was stirred at room temperature for 2 h then more sodium hydride (50 mg of a 60% dispersion in mineral oil, 1.3 mmol) and ethyl formate (0.55 mL, 6.8 mmol) were added. The mixture was stirred for a further 2 h before MeOH (0.2 mL) was added and the mixture evaporated in vacuo. The residue was dissolved in water (20 mL) and the undissolved solid filtered off. The mixture was acidified to pH 1 using 1M HCl then neutralised with Na2CO3. The mixture was partitioned between EtOAc (20 mL) and water (10 mL) and the organic layer separated and dried (MgSO4). The solvent was evaporated and the residue triturated with ether to afford the title compound (90 mg, 40%) as a yellow solid. 1H NMR (250 MHz, CDCl3) δ1.21 (6H, s), 2.70 (3H, s), 2.93 (2H, s), 7.16-7.22 (1H, m), 7.4.3 (1H, d, J=8.0 Hz), 7.57 (1H, d, J=10.4 Hz), 7.74 (1H, d of t, J=7.7 and 1.8 Hz), 8.62-8.65 (1H, m), 14.68 (1H, d, J=10.4 Hz). MS (ES+) 332 (M+1).
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([CH3:9])[N:3]=1.[Br:10][C:11]1[CH:12]=[C:13]([C:17]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:26]=2[C:32]#[N:33])=[N:18]S(C(C)(C)C)=O)[CH:14]=[CH:15][CH:16]=1>>[Br:10][C:11]1[CH:12]=[C:13]([C:17]2([C:2]3[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([CH3:9])[N:3]=3)[C:25]3[C:26](=[C:27]([F:31])[CH:28]=[CH:29][CH:30]=3)[C:32]([NH2:33])=[N:18]2)[CH:14]=[CH:15][CH:16]=1
Reactant: CC(C)(C)S(=O)N=C(c1cccc(Br)c1)c1cccc(F)c1C#N
Reactant: Cc1cc(Br)nc(C)n1
Product: Cc1cc(C2(c3cccc(Br)c3)N=C(N)c3c(F)cccc32)nc(C)n1
Yield: 35 %

Procedure:
The title compound was synthesized as described for Example 35i in 35% yield, starting from of 4-bromo-2,6-dimethylpyrimidine (507 mg, 2.71 mmol) and N-((3-bromophenyl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide (850 mg, 2.09 mmol). MS (ES+) m/z 411, 413 [M+H]+.
Reaction SMILES: [CH2:1]([N:8]1[C:14](=[O:15])[C@H:13]2[CH2:16][CH2:17][CH2:18][C@H:12]2[NH:11][C:10]2[CH:19]=[CH:20][CH:21]=[CH:22][C:9]1=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23](OC(=O)C)(=[O:25])[CH3:24]>>[C:23]([N:11]1[C@@H:12]2[CH2:18][CH2:17][CH2:16][C@@H:13]2[C:14](=[O:15])[N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:9]2[CH:22]=[CH:21][CH:20]=[CH:19][C:10]1=2)(=[O:25])[CH3:24]
Reactant: O=C1[C@H]2CCC[C@H]2Nc2ccccc2N1Cc1ccccc1
Reactant: CC(=O)OC(C)=O
Product: CC(=O)N1c2ccccc2N(Cc2ccccc2)C(=O)[C@H]2CCC[C@H]21
Temperature: 100 °C
Reaction time: 0.58 h
Yield: 77 %

Procedure:
A mixture of (3aR*,10aS*)-9-benzyl-2,3,3a,4,9,10a-hexahydrobenzo[b]cyclopenta[e][1,4]diazepin-10(1H)-one (1.47 g, 5.0 mmol) and acetic anhydride (5 mL) was stirred for 35 minutes at 100° C. Resulting crystalline precipitate was collected by filtration, which was washed with ethanol to give 1.29 g (yield 77%) of the titled compound, m.p. 209°-210° C.
Reaction SMILES: N[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:23][C@H:22]([CH2:24][O:25][C:26](=[O:28])[CH3:27])[C@@H:17]([O:18][C:19](=[O:21])[CH3:20])[C@H:12]2[O:13][C:14](=[O:16])[CH3:15])=[C:4]([Cl:29])[N:3]=1.N(OC(C)(C)C)=[O:31]>CC(O)C.O>[Cl:29][C:4]1[N:3]=[C:2]([OH:31])[N:10]=[C:9]2[C:5]=1[N:6]=[CH:7][N:8]2[C@@H:11]1[O:23][C@H:22]([CH2:24][O:25][C:26](=[O:28])[CH3:27])[C@@H:17]([O:18][C:19](=[O:21])[CH3:20])[C@H:12]1[O:13][C:14](=[O:16])[CH3:15]
Reactant: CC(C)(C)ON=O
Reactant: CC(=O)OC[C@H]1O[C@@H](n2cnc3c(Cl)nc(N)nc32)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Solvent: O
Solvent: CC(C)O
Product: CC(=O)OC[C@H]1O[C@@H](n2cnc3c(Cl)nc(O)nc32)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: 25 °C

Procedure:
A suspension of 2-amino-6-chloro-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine (291.2 g, 0.68 mol, Example 1, Step B) in 2-propanol and water (1:1, 15,560 mL) which was heated to achieve homogeneity. The solution was cooled to <15° C. and then t-butyl nitrite (357 mL, 3.0 mol) was added. The reaction was allowed to warm to room temperature and stirred until the evolution of gas subsided. The reaction was partitioned between ethyl acetate (7,300 mL) and water and the phases allowed to separate. The aqueous layer was further extracted with ethyl acetate (2×7,300 mL) and the combined organic layers were dried over magnesium sulfate, filtered and removed under reduced pressure to yield a viscous oil. Typical Yield: Quantitative.
Reaction SMILES: [F:1][CH:2]([F:26])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:18]=[CH:17][CH:16]=[C:15]3[C:11]=2[CH2:12][CH2:13][C:14]3=[O:19])=[C:6]([O:20]COC)[C:5]=1[O:24][CH3:25].Cl>CO>[F:1][CH:2]([F:26])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:18]=[CH:17][CH:16]=[C:15]3[C:11]=2[CH2:12][CH2:13][C:14]3=[O:19])=[C:6]([OH:20])[C:5]=1[O:24][CH3:25]
Reactant: COCOc1c(-c2cccc3c2CCC3=O)ccc(OC(F)F)c1OC
Agent: Cl
Solvent: CO
Product: COc1c(OC(F)F)ccc(-c2cccc3c2CCC3=O)c1O
Temperature: 50 °C
Yield: 79.8 %

Procedure:
To a stirring solution of 4-(4-(difluoromethoxy)-3-methoxy-2-(methoxymethoxy)phenyl)-2,3-dihydro-1H-inden-1-one (1 g, 2.74 mmol) in methanol (75 mL) was added concentrated hydrochloride (5 mL) and the reaction mixture was heated to 50° C. for 1 h. The reaction mixture was cooled to RT and concentrated under reduced pressure and the obtained residue was basified with sodium bicarbonate solution and extracted with dichloromethane (3×). The combined dichloromethane layers were washed with brine, dried over sodium sulphate and concentrated under reduced pressure to afford the title compound as a solid (700 mg, 80%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:28](=[O:29])[N:27]([CH3:30])[C:12]2[N:13]([CH3:26])[C:14]3[C:19]([C:11]=2[CH:10]=1)=[CH:18][C:17]([C:20]1[NH:24][N:23]=[C:22]([CH3:25])[CH:21]=1)=[CH:16][CH:15]=3.I[CH2:32][CH3:33]>>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:28](=[O:29])[N:27]([CH3:30])[C:12]2[N:13]([CH3:26])[C:14]3[C:19]([C:11]=2[CH:10]=1)=[CH:18][C:17]([C:20]1[CH:21]=[C:22]([CH3:25])[N:23]([CH2:32][CH3:33])[N:24]=1)=[CH:16][CH:15]=3
Reactant: Cc1cc(-c2ccc3c(c2)c2cc(-c4ccc(Cl)cc4Cl)c(=O)n(C)c2n3C)[nH]n1
Reactant: CCI
Product: CCn1nc(-c2ccc3c(c2)c2cc(-c4ccc(Cl)cc4Cl)c(=O)n(C)c2n3C)cc1C

Procedure:
The process is carried out as indicated in Example 36 above, using 3-(2,4-dichlorophenyl)-1,9-dimethyl-6-(3-methyl-1H-pyrazol-5-yl)-1,9-dihydro-2H-pyrido[2,3-b]indol-2-one described in Example 46 above and iodoethane.
Reaction SMILES: [Si]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][O:17][CH2:18]/[CH:19]=[CH:20]\[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])=[CH:12][CH:11]=1)(C(C)(C)C)(C)C.C([O-])(O)=O.[Na+].CCOCC>CC#N>[CH2:18]([O:17][CH2:16][C:13]1[CH:14]=[CH:15][C:10]([CH2:9][OH:8])=[CH:11][CH:12]=1)/[CH:19]=[CH:20]\[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]
Reactant: CCCCCCCCCC/C=C\COCc1ccc(CO[Si](C)(C)C(C)(C)C)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC#N
Solvent: CCOCC
Product: CCCCCCCCCC/C=C\COCc1ccc(CO)cc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 108.4 %

Procedure:
To a solution of silyl ether (41) (341 mg, 0.84 mmol) in CH3CN (10 mL) was added 50% aqueous HF (1 mL) the mixture was stirred at room temperature for 15 minutes. The reaction mixture was poured into saturated aqueous NaHCO3 (50 mL) and ether (75 mL). The organic layer was separated and washed with two 50-mL portions of water, dried (MgSO4), and concentrated to yield (42) (290 mg, 98%) as a colorless oil: Rf 0.24 (9:1 petroleum ether/EtOAc); 1H NMR (CDCl3) δ 7.30 (s, 4 H), 5.60 (m, 2 H), 4.63 (s, 2 H), 4.49 (s, 2 H), 4.07 (d, J=5.1 Hz, 2 H), 239 (s, 2 H), 2.04 (q, J=6.6 Hz, 2 H), 1.27 (m, 16 H), 0.89 (t, J 6.6 Hz, 2 H); 13C NMR (CDCl3) δ 140.49, 137.82, 134.24, 128.10, 127.12, 125.94, 71.88, 65.85, 65.03, 32.03, 29.76, 29.66, 29.48, 29.37, 27.73, 22.82, 14.24. ##STR9##
Reaction SMILES: [Cl:1][C:2]1[CH:37]=[CH:36][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([O:16][CH2:17][C:18]4[CH:27]=[CH:26][C:25]5[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=5)[N:19]=4)=[CH:13][CH:14]=3)[CH:9]=[C:8]2[CH2:28][C:29]([CH3:35])([CH3:34])[C:30]([O:32]C)=[O:31])=[CH:4][CH:3]=1.[C:38]1([CH2:44][C:45](Cl)=[O:46])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([O:16][CH2:17][C:18]4[CH:27]=[CH:26][C:25]5[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=5)[N:19]=4)=[CH:13][CH:14]=3)[C:9]([C:45](=[O:46])[CH2:44][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)=[C:8]2[CH2:28][C:29]([CH3:35])([CH3:34])[C:30]([OH:32])=[O:31])=[CH:36][CH:37]=1
Reactant: O=C(Cl)Cc1ccccc1
Reactant: COC(=O)C(C)(C)Cc1cc2cc(OCc3ccc4ccccc4n3)ccc2n1Cc1ccc(Cl)cc1
Product: CC(C)(Cc1c(C(=O)Cc2ccccc2)c2cc(OCc3ccc4ccccc4n3)ccc2n1Cc1ccc(Cl)cc1)C(=O)O

Procedure:
The title compound was prepared according to the conditions described in Step B and Step C of Example 47, from methyl 3-[N-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoate (prepared in Step A of Example 47), but using phenylacetyl chloride in place of trimethylacetyl chloride in Step B.
Reaction SMILES: [NH2:1][C:2]1[NH:3][C:4](=[S:16])[C:5]([C:14]#[N:15])=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:7]=1.[CH2:17](Br)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.CC[O-].[Na+]>C(O)C>[NH2:1][C:2]1[N:3]=[C:4]([S:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:5]([C:14]#[N:15])=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:7]=1
Reactant: BrCc1ccccc1
Reactant: N#Cc1c(-c2ccccc2)nc(N)[nH]c1=S
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: N#Cc1c(SCc2ccccc2)nc(N)nc1-c1ccccc1

Procedure:
From 2-amino-4-phenyl-6-thioxo-1,6-dihydro-pyrimidine-5-carbonitrile, benzyl bromide and sodium ethylate in ethanol. EI-MS m/e (%):318 (M+, 50), 317 ([M—H]+, 100), 285 (20), 91 (84).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([N+:13]([O-])=O)[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[Cl-].[NH4+].O>CO.[Fe]>[NH2:13][C:4]1[C:5]([CH3:12])=[C:6]([CH:11]=[C:2]([Br:1])[CH:3]=1)[C:7]([O:9][CH3:10])=[O:8]
Reactant: COC(=O)c1cc(Br)cc([N+](=O)[O-])c1C
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CO
Solvent: O
Product: COC(=O)c1cc(Br)cc(N)c1C
Temperature: 70 °C
Reaction time: 2 h
Yield: 58.5 %

Procedure:
To a solution of methyl 5-bromo-2-methyl-3-nitrobenzoate (6.3 g, 21 mmol) in methanol (150 ml) was added ammonium chloride (11.0 g, 210 mmol) followed by deionized water (75 ml). The mixture was heated to 70° C. before the addition of iron (7.0 g, 125 mmol). The reaction mixture was stirred at 70° C. for 2 hours, before being allowed to cool to room temperature and filtered through Kieselgel. The filter pad was washed with MeOH (150 ml) and the filtrate concentrated in-vacuo. The residue was dissolved in saturated NaHCO3 (aq) (50 ml) and EtOAc (150 ml). The phases were separated and the organic phase was washed with saturated NaHCO3 (aq) (3×50 ml), dried over MgSO4, filtered and concentrated in-vacuo. The residue was purified by flash column chromatography (50 g silica Isolute cartridge, 5-20% EtOAc:Heptanes) to give the title compound (3.0 g, 51%) as a thick pale yellow oil. LC-MS 87%, m/z=243.9, 244.9, 245.9, 246.9; 1H NMR (500 MHz, Chloroform-d) δ ppm 7.34 (d, J=1.89 Hz, 1H) 6.95 (d, J=1.89 Hz, 1H) 3.88 (s, 3H) 3.80 (br. s., 2H) 2.29 (s, 3H).
Reaction SMILES: [CH:1]1([C:7]#[C:8][C:9]2[CH:10]=[N:11][C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([O:19][CH3:20])=[C:14]([O:21][CH3:22])[CH:13]=3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1>CO.C(O)(=O)C.[Pd]>[CH:1]1([CH2:7][CH2:8][C:9]2[CH:10]=[N:11][C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([O:19][CH3:20])=[C:14]([O:21][CH3:22])[CH:13]=3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: COc1cc2cc(C#CC3CCCCC3)cnc2cc1OC
Agent: [Pd]
Solvent: CO
Solvent: CC(=O)O
Product: COc1cc2cc(CCC3CCCCC3)cnc2cc1OC

Procedure:
To 3-cyclohexylethynyl-6,7-dimethoxyquinoline (215 mg; 0.73 mmol) in 10 mL CH3OH and 20 mL glacial acetic acid is added 22 mg 10% Pd/C. H2 is bubbled through the reaction mixture and then filtered, evaporated to dryness and diluted with distilled water. This is then neutralized with Na2CO3, extracted with EtOAc, washed with brine, dried (MgSO4), evaporated to dryness and chromatographed with 8:2/hexane: EtOAc to obtain 3-cyclohexylethyl-6,7-dimethoxyquinoline.
Reaction SMILES: [C:1]([NH:4][C:5]1[S:6][CH:7]=[C:8]([C:10]([OH:12])=[O:11])[N:9]=1)(=[O:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.O[C:26]1[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][NH:34][C:35]([NH:37][NH:38][C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])=[O:36])=[CH:28][CH:27]=1.O>C(OCC)(=O)C>[C:1]([NH:4][C:5]1[S:6][CH:7]=[C:8]([C:10]([O:12][C:26]2[CH:27]=[CH:28][C:29]([CH2:32][CH2:33][NH:34][C:35]([NH:37][NH:38][C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])=[O:36])=[CH:30][CH:31]=2)=[O:11])[N:9]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)Nc1nc(C(=O)O)cs1
Reactant: CC(C)(C)OC(=O)NNC(=O)NCCc1ccc(O)cc1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: O
Solvent: CCOC(C)=O
Product: CC(=O)Nc1nc(C(=O)Oc2ccc(CCNC(=O)NNC(=O)OC(C)(C)C)cc2)cs1
Temperature: 50 °C
Reaction time: 2 h
Yield: 44.4 %

Procedure:
To a suspension of 2-(acetylamino)-1,3-thiazole-4-carboxylic acid (559.5 mg, 3.005 mmol) in anhydrous N,N-5 dimethylformamide (10 ml) was added 1,1′-carbonyldiimidazole (534.2 mg, 3.294 mmol), and the mixture was stirred at 50° C. for 2 hr. tert-Butyl 2-{[2-(4-hydroxyphenyl)ethyl]carbamoyl}hydrazinecarboxylate (591.6 mg, 2.003 mmol) was added, and the mixture was stirred at 50° C. for 24 hr and at room temperature for 17 hr. Water (50 ml) and ethyl acetate (50 ml) were added to the reaction mixture and the mixture was stirred, stood still and then partitioned. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with 0.5M hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Methanol (20 ml) and tert-butyl methyl ether (40 ml) were added to the residue and the precipitated solid was collected by filtration and dried under reduced pressure to give 4-[2-({[2-(tert-butoxycarbonyl)hydrazino]carbonyl}amino)ethyl]phenyl 2-(acetylamino)-1,3-thiazole-4-carboxylate (417.7 mg, 0.890 mmol, yield 44.5%) as a white solid.