Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]([CH2:17][CH2:18][CH:19]([C:31]1[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=1)[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([O:27]COC)=[CH:23][CH:22]=1)[S:7]([C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=1)(=[O:9])=[O:8])=[O:5])[CH3:2].Cl>CO>[CH2:1]([O:3][C:4]([N:6]([CH2:17][CH2:18][CH:19]([C:31]1[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=1)[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=1)[S:7]([C:10]1[CH:11]=[CH:12][C:13]([Cl:16])=[CH:14][CH:15]=1)(=[O:9])=[O:8])=[O:5])[CH3:2]
Reactant: CCOC(=O)N(CCC(Cc1ccc(OCOC)cc1)c1cccnc1)S(=O)(=O)c1ccc(Cl)cc1
Agent: Cl
Solvent: CO
Product: CCOC(=O)N(CCC(Cc1ccc(O)cc1)c1cccnc1)S(=O)(=O)c1ccc(Cl)cc1
Temperature: 60 °C
Reaction time: 0.75 h
Yield: 94.9 %

Procedure:
In argon atmosphere, 0.54 g of N-ethoxycarbonyl-N-[4-(4-methoxymethyloxyphenyl)-3-(3-pyridyl)butyl]-4-chlorobenzene sulfonamide was dissolved in 15 ml of methanol, followed by addition of 1 ml of 6N hydrogen chloride, and stirred at 60 ° C. for 45 minutes. After completion of the reaction, the solvent was distilled off under reduced pressure, followed by addition of methylene chloride and further by addition of saturated aqueous sodium hydrogencarbonate so that the resulting mixture became weak alkaline. The organic phase was separated, which was then extracted with methylene chloride. The organic phases combined were washed in saturated aqueous sodium chloride and dried over magnesium sulfate. After the evaporation of the solvent, 0.47 g of N-ethoxycarbonyl-N-[4-(4-hydroxyphenyl)-3-(3-pyridyl)butyl]-4-chlorobenzenesulfonamide was produced.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[NH:12][CH:11]=[C:10]([CH:13]=[O:14])[CH:9]=1.[O-]S(C(F)(F)[F:20])(=O)=O.ClC1C=CC=C(Cl)[N+]=1F.C(=O)([O-])O.[Na+]>O1CCCC1>[F:20][C:9]1[C:10]([CH:13]=[O:14])=[CH:11][NH:12][C:8]=1[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[F:1]
Reactant: O=S(=O)([O-])C(F)(F)F
Reactant: O=Cc1c[nH]c(-c2ccccc2F)c1
Agent: F[n+]1c(Cl)cccc1Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: O=Cc1c[nH]c(-c2ccccc2F)c1F
Reaction time: 2 h
Yield: 12.7 %

Procedure:
To a solution (60 mL) of 5-(2-fluorophenyl)-1H-pyrrole-3-carbaldehyde (3.1 g) in tetrahydrofuran was added 2,6-dichloro-N-fluoropyridinium triflate (5.6 g) at 0° C., and the mixture was stirred at the same temperature for 2 hr. Saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate=2:1) to give the title compound as white crystals (yield 0.43 g, 13%).
Reaction SMILES: [CH:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:12][C:13]3[CH:19]=[CH:18][CH:17]=[CH:16][C:14]=3[N:15]=2)=[CH:7][C:6]=1[N+:20]([O-])=O)([CH3:3])[CH3:2].[H][H]>[C].[Pd].O1CCCC1>[CH:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:12][C:13]3[CH:19]=[CH:18][CH:17]=[CH:16][C:14]=3[N:15]=2)=[CH:7][C:6]=1[NH2:20])([CH3:3])[CH3:2]
Reactant: CC(C)Nc1ccc(-c2nc3ccccc3o2)cc1[N+](=O)[O-]
Reactant: [H][H]
Agent: [Pd]
Solvent: C1CCOC1
Product: CC(C)Nc1ccc(-c2nc3ccccc3o2)cc1N
Temperature: 25 °C
Reaction time: 15 h
Yield: 91.4 %

Procedure:
To a tetrahydrofuran solution (5 mL) of 2-(4-isopropylamino-3-nitrophenyl)benzoxazole (see Working Example 80-1) (224 mg, 0.753 mmol) was added 10% palladium-carbon (40 mg), a hydrogen atmosphere was substituted in the flask, and this was stirred at room temperature for 15 hours. After the reaction was complete, this was filtered through Celite and the filtrate was concentrated. The residue obtained was purified by silica gel column chromatography to yield the title compound (184 mg, 91% yield).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:32])[C:10]3([CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][C:13](=[O:23])[NH:12][CH:11]3[C:24]3[CH:29]=[C:28](I)[CH:27]=[CH:26][C:25]=3[F:31])[C:5]2=[CH:4][CH:3]=1.C[Si]([C:37]#[CH:38])(C)C.C(N(CC)CC)C.[OH-].[Na+]>CN(C)C=O.CO.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:32])[C:10]3([CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][C:13](=[O:23])[NH:12][CH:11]3[C:24]3[CH:29]=[C:28]([C:37]#[CH:38])[CH:27]=[CH:26][C:25]=3[F:31])[C:5]2=[CH:4][CH:3]=1
Reactant: O=C1CC(c2cccc(Cl)c2)C2(C(=O)Nc3cc(Cl)ccc32)C(c2cc(I)ccc2F)N1
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CO
Solvent: CN(C)C=O
Product: C#Cc1ccc(F)c(C2NC(=O)CC(c3cccc(Cl)c3)C23C(=O)Nc2cc(Cl)ccc23)c1
Yield: 15.4 %

Procedure:
In a manner similar to the method described in example 193, racemic (2′S,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-2′-(2-fluoro-5-iodophenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione prepared in example 194b (0.45 g, 0.77 mmol) was reacted with trimethylsilyl acetylene (1.1 mL, 7.7 mmol), CuI (10 mg), triethylamine (3.22 mL, 23 mmol), and dichlorobis(triphenylphosphine)palladium (54 mg, 0.077 mmol) in anhydrous N,N-dimethylformamide, and then treated with aqueous NaOH in methanol to give racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-2′-(5-ethynyl-2-fluoro-phenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione as a light brown solid (Yield 57 mg)
Reaction SMILES: [NH2:1][CH:2]1[CH2:6][CH2:5][CH2:4][C:3]1([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH3:7].CCN(C(C)C)C(C)C.Cl[C:26]([O:28][C@@H:29]1[CH2:34][C@H:33]([CH3:35])[CH2:32][CH2:31][C@H:30]1[CH:36]([CH3:38])[CH3:37])=[O:27].C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:11]([O:10][C:9]([NH:8][C:3]1([CH3:7])[CH2:4][CH2:5][CH2:6][CH:2]1[NH:1][C:26](=[O:27])[O:28][C@@H:29]1[CH2:34][C@H:33]([CH3:35])[CH2:32][CH2:31][C@H:30]1[CH:36]([CH3:38])[CH3:37])=[O:15])([CH3:14])([CH3:13])[CH3:12]
Reactant: CC(C)(C)OC(=O)NC1(C)CCCC1N
Reactant: CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OC(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OC(=O)NC1CCCC1(C)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of tert-butyl N-(2-amino-1-methylcyclopentyl)carbamate (Intermediate 24; 5.49 ml, 26.1 mmol) in DCM (87 ml) at 0° C. was added DIPEA (4.56 ml, 26.1 mmol) followed by (1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl chloroformate (CAS number 14602-86-9; 17.15 g, 78 mmol) drop wise. The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction was diluted with DCM (150 ml) and a saturated solution of sodium bicarbonate solution (200 ml). The aqueous layer was re-extracted with DCM (100 ml) and the combined organics were washed further with a saturated solution of sodium bicarbonate (100 ml), dried over magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography (silica, 0-50% ethyl acetate/petrol) to afford the title compound.
Reaction SMILES: C([O:8][C@H:9]([C@H:11]([N:22]1[CH:26]=[C:25]([C:27]([NH2:29])=[O:28])[N:24]=[CH:23]1)[CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[S:20][CH3:21])[CH3:10])C1C=CC=CC=1.I[Si](C)(C)C.CO>C(Cl)(Cl)Cl>[OH:8][C@H:9]([C@H:11]([N:22]1[CH:26]=[C:25]([C:27]([NH2:29])=[O:28])[N:24]=[CH:23]1)[CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[S:20][CH3:21])[CH3:10]
Reactant: CSc1ccccc1CC[C@H]([C@H](C)OCc1ccccc1)n1cnc(C(N)=O)c1
Agent: C[Si](C)(C)I
Solvent: ClC(Cl)Cl
Solvent: CO
Product: CSc1ccccc1CC[C@H]([C@H](C)O)n1cnc(C(N)=O)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 59.8 %

Procedure:
A mixture of 1-[(2S,3R)-2-(benzyloxy)-5-(2-(methylthio)phenyl)-3-pentyl]imidazole-4-carboxamide (133 mg) and iodotrimethylsilane (0.16 ml) in chloroform (5 ml) was stirred at room temperature for 2 hours. The mixture was poured into cold methanol and the whole was evaporated in vacuo. The residue was taken up in ethyl acetate, washed with water, aqueous sodium bisulfite and sodium bicarbonate, successively, and dried. The residue left after evaporation of solvent was purified by column chromatography on silica gel, eluting with a mixture of dichloromethane and methanol (20:1) to give a white powder of 1-[(2S,3R)-2-hydroxy-5-(2-(methylthio)phenyl)-3-pentyl]imidazole-4-carboxamide (2) (62 mg).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[C:10]([F:13])([F:12])[F:11].[CH2:14](Br)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH2:14]([O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[C:10]([F:11])([F:12])[F:13])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: BrCc1ccccc1
Reactant: O=Cc1ccc(O)c(C(F)(F)F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: O=Cc1ccc(OCc2ccccc2)c(C(F)(F)F)c1
Yield: 75.8 %

Procedure:
A solution of 4-hydroxy-3-(trifluoromethyl)benzaldehyde (1.5 g, 8.0 mmol), benzyl bromide (1.51 g, 8.8 mmol) and potassium carbonate (1.66 g, 12.0 mmol) in dimethyl formamide (20 mL) was stirred water (100 mL) and extracted 3 times with ethyl acetate. The ethyl acetate extracts were combined and washed 2 times with water and dried over magnesium sulfate. Concentration in vacuo yielded 1.7 g of 4-benzyloxy-3-trifluoromethyl-benzaldehyde which was used as such in the next step.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:14]([NH2:23])=[N:13][CH:12]=2)([CH3:10])[CH3:9])=[CH:4][C:3]=1[O:24][CH3:25].N1C=CC=CC=1.[Cl:32][C:33]1[CH:41]=[CH:40][CH:39]=[C:38]([F:42])[C:34]=1[C:35](Cl)=[O:36]>C(Cl)Cl>[Cl:32][C:33]1[CH:41]=[CH:40][CH:39]=[C:38]([F:42])[C:34]=1[C:35]([NH:23][C:14]1[N:15]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[C:11]([C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([O:24][CH3:25])[CH:4]=2)([CH3:10])[CH3:9])=[CH:12][N:13]=1)=[O:36]
Reactant: O=C(Cl)c1c(F)cccc1Cl
Reactant: COc1cc(C(C)(C)c2cnc(N)n2-c2ccc(F)cc2)ccc1Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: COc1cc(C(C)(C)c2cnc(NC(=O)c3c(F)cccc3Cl)n2-c2ccc(F)cc2)ccc1Cl
Temperature: 25 °C
Reaction time: 2 h
Yield: 6.7 %

Procedure:
To a 0° C. solution of 5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-amine (93 mg, 0.26 mmol) and pyridine (0.05 mL, 0.52 mmol) in DCM (1.5 mL) was added 2-chloro-6-fluorobenzoyl chloride (0.050 g, 0.26 mmol) in DCM (0.5 mL). After stirring 2 h at ambient temperature, the reaction was quenched with water. The mixture was extracted with DCM (3×5 mL) and dried with MgSO4. The residue was purified by HPLC (10-99%, MeCN/H2O with 0.05% TFA) to afford the title compound (9 mg) as a white solid. MS (EI) m/z 516 [M+H]+.
Reaction SMILES: C([O-])(=O)C.[NH4+].[BH3-][C:7]#[N:8].[Na+].C[C:11]([C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([N+:20]([O-:22])=[O:21])[CH:14]=1)=O.C([O-])(O)=O.[Na+]>CO.CCOC(C)=O>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]([CH3:11])([CH2:7][NH2:8])[CH2:14][C:15]=1[N+:20]([O-:22])=[O:21]
Reactant: [BH3-]C#N
Reactant: CC(=O)c1ccc(Cl)c([N+](=O)[O-])c1
Agent: CC(=O)[O-]
Agent: O=C([O-])O
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: CO
Product: CC1(CN)C=CC(Cl)=C([N+](=O)[O-])C1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
Ammonium acetate (3.86 g, 50 mmol), NaBH3CN (0.22 g, 3.5 mmol), and 3 Å molecular sieves (25 g) were added to a mixture of 4-chloro-3-nitroacetophenone (1.00 g, 5 mmol) in MeOH (15 mL) at rt. The mixture was stirred at rt for 20 h and NaHCO3 (aq, sat) and EtOAc were added. The mixture was filtered and the aq layer washed with EtOAc. The combined organic phases were dried over Na2SO4 and concentrated to give the sub-title compound. Yield: 0.27 g (27%).
Reaction SMILES: [CH3:1]/[C:2](=[CH:6]\[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)/[C:3]([OH:5])=O.C(Cl)(=O)C(Cl)=O.[N:19]([CH2:22][CH2:23][NH2:24])=[N+:20]=[N-:21].C(N(CC)CC)C>ClCCl>[N:19]([CH2:22][CH2:23][NH:24][C:3](=[O:5])/[C:2](/[CH3:1])=[CH:6]/[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[N+:20]=[N-:21]
Reactant: [N-]=[N+]=NCCN
Reactant: C/C(=C\c1ccccc1)C(=O)O
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C/C(=C\c1ccccc1)C(=O)NCCN=[N+]=[N-]
Reaction time: 1 h
Yield: 96.2 %

Procedure:
To a 25 mL round-bottomed flask equipped with a magnetic stir bar was added (E)-2-methyl-3-phenylacrylic acid (0.0.512 g, 3.15 mmol) and dichloromethane (10 mL). Oxalyl chloride (0.400 g, 3.15 mmol) was added dropwise to the reaction mixture and allowed to stir for one hour. Then, the reaction mixture was concentrated de vacuo. To the crude mixture was then added dichloromethane (10 mL), 2-azidoethanamine (0.299 g, 3.47 mmol) and then triethylamine (0.351 g, 3.47 mmol) and allowed to stir for two hours. The reaction mixture was then concentrated de vacuo and then purified via silica gel column chromatography (100% dichloromethane to 1:40 methanol:dichloromethane) to give (E)-N-(2-azidoethyl)-2-methyl-3-phenylacrylamide (0.698 g, 96% yield). 1H NMR (300 MHz, CDCl3) δ 7.39 (m, 6H), δ 7.01 (s, 1H), δ 3.51 (t, 2H), δ 3.45 (t, 2H), δ 2.13 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3) δ 170.5, 136.2, 134.5, 132.0, 130.3, 129.6, 128.9, 128.6, 128.3, 50.9, 39.8, 14.5 ppm; HRMS (ESI) calcd for C12H14N4O (M+) 230.1168. Found 230.1165.
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].[CH3:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][C:16](=[O:18])[CH3:17])[C:7]=1[C:8]([OH:10])=[O:9]>O>[CH3:5][C:6]1[C:14]([N+:1]([O-:4])=[O:2])=[CH:13][CH:12]=[C:11]([NH:15][C:16](=[O:18])[CH3:17])[C:7]=1[C:8]([OH:10])=[O:9]
Reactant: CC(=O)Nc1cccc(C)c1C(=O)O
Reactant: O=[N+]([O-])O
Solvent: O
Product: CC(=O)Nc1ccc([N+](=O)[O-])c(C)c1C(=O)O
Temperature: 10 °C
Reaction time: 1 h

Procedure:
271 ml of 98 percent nitric acid are initially taken at -5° C. and 106 g (0.55 mol) of the 2-methyl-6-acetamidobenzoic acid prepared in 1. are added in portions. After stirring at 10° C. for one hour, the reaction mixture is poured into a mixture of 540 g of ice and 270 ml of water. The deposited precipitate is filtered off with suction, washed with water and dried under reduced pressure at 50° C.
Reaction SMILES: Cl[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1([NH:14][C:15]2[C:16](=[O:35])[N:17]([C:21]3[CH:22]=[C:23]([CH:30]=[C:31]([F:34])[C:32]=3[CH3:33])[C:24]([NH:26][CH:27]3[CH2:29][CH2:28]3)=[O:25])[CH:18]=[CH:19][N:20]=2)[CH2:13][CH2:12]1.[CH3:36][NH2:37]>O1CCOCC1>[CH:27]1([NH:26][C:24](=[O:25])[C:23]2[CH:22]=[C:21]([N:17]3[CH:18]=[CH:19][N:20]=[C:15]([NH:14][C:11]4([C:6]5[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=5[O:4][CH2:3][CH2:2][NH:37][CH3:36])[CH2:13][CH2:12]4)[C:16]3=[O:35])[C:32]([CH3:33])=[C:31]([F:34])[CH:30]=2)[CH2:29][CH2:28]1
Reactant: CN
Reactant: Cc1c(F)cc(C(=O)NC2CC2)cc1-n1ccnc(NC2(c3ccccc3OCCCl)CC2)c1=O
Solvent: C1COCCO1
Product: CNCCOc1ccccc1C1(Nc2nccn(-c3cc(C(=O)NC4CC4)cc(F)c3C)c2=O)CC1
Temperature: 100 °C
Reaction time: 16 h

Procedure:
3-[3-[[1-[2-(2-chloroethoxy)phenyl]cyclopropyl]amino]-2-oxo-1(2H)-pyrazinyl]-N-cyclopropyl-5-fluoro-4-methyl-benzamide (Example 259d, 10 g) in dioxane (25 mL) was treated with methylamine (15 mL of a 40 wt % aqueous solution). The resulting mixture was stirred at 100° C. for 16 h in a sealed tube. The reaction mixture was cooled, filtered and the solvents removed in vacuo to give crude product (˜10 g). The crude product (˜8.0 g) was purified by RPHPLC (Waters X-Bridge column, 95-5% gradient of aqueous 0.2% ammonia in acetonitrile as mobile phase). The product containing fractions were combined, evaporated and triturated with diethyl ether overnight. The white solid was collected by filtration and dried in vacuo to afford the title compound (4.14 g). NMR consistent with that described above in example 259.
Reaction SMILES: C([N:4]1[CH2:8][CH2:7][N:6]=[C:5]1[NH:9][C:10]1[N:14]([CH:15]([CH3:17])[CH3:16])[N:13]=[C:12]([CH3:18])[CH:11]=1)(=O)C.Cl>CO>[CH:15]([N:14]1[C:10]([NH:9][C:5]2[NH:6][CH2:7][CH2:8][N:4]=2)=[CH:11][C:12]([CH3:18])=[N:13]1)([CH3:17])[CH3:16]
Reactant: CC(=O)N1CCN=C1Nc1cc(C)nn1C(C)C
Agent: Cl
Solvent: CO
Product: Cc1cc(NC2=NCCN2)n(C(C)C)n1
Yield: 77.8 %

Procedure:
1-acetyl-2-(1-isopropyl-3-methyl-5-pyrazolyl) amino-2-imidazoline (14.0 g.) was treated with HCl in methanol as described in Example II to give 9.05 g of product, mp 173°-175° C.
Reaction SMILES: [C:1]([O:9][C@@H:10]1[C@@H:24]([O:25][C@@H:26]2[O:55][C@@H:54]([CH3:56])[C@@H:45]([O:46][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[C@@H:36]([O:37][CH2:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[C@@H:27]2[O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C@H:23]([O:57][C@@H:58]2[O:74][C@H:73]([CH2:75][O:76][C:77](=[O:84])[C:78]3[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=3)[C@H:71]([OH:72])[C@H:69]([OH:70])[C@H:59]2[O:60][C:61](=[O:68])[C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[C@@H:22]([CH2:85][O:86][C:87](=[O:94])[C:88]2[CH:93]=[CH:92][CH:91]=[CH:90][CH:89]=2)[O:21][C@H:11]1[O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=CC=CC=1.C([C:103](CC)(CC)[C:104]([O-])([O-])[O-:105])C.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(N(CC)CC)C>[C:1]([O:9][C@@H:10]1[C@@H:24]([O:25][C@@H:26]2[O:55][C@@H:54]([CH3:56])[C@@H:45]([O:46][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[C@@H:36]([O:37][CH2:38][C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=3)[C@@H:27]2[O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C@H:23]([O:57][C@@H:58]2[O:74][C@H:73]([CH2:75][O:76][C:77](=[O:84])[C:78]3[CH:79]=[CH:80][CH:81]=[CH:82][CH:83]=3)[C@H:71]([O:72][C:104](=[O:105])[CH3:103])[C@H:69]([OH:70])[C@H:59]2[O:60][C:61](=[O:68])[C:62]2[CH:63]=[CH:64][CH:65]=[CH:66][CH:67]=2)[C@@H:22]([CH2:85][O:86][C:87](=[O:94])[C:88]2[CH:89]=[CH:90][CH:91]=[CH:92][CH:93]=2)[O:21][C@H:11]1[O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCC(CC)(CC)C([O-])([O-])[O-]
Reactant: CCCCCCCCO[C@@H]1O[C@H](COC(=O)c2ccccc2)[C@@H](O[C@@H]2O[C@H](COC(=O)c3ccccc3)[C@H](O)[C@H](O)[C@H]2OC(=O)c2ccccc2)[C@H](O[C@@H]2O[C@@H](C)[C@@H](OCc3ccccc3)[C@@H](OCc3ccccc3)[C@@H]2OCc2ccccc2)[C@H]1OC(=O)c1ccccc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCN(CC)CC
Solvent: c1ccccc1
Product: CCCCCCCCO[C@@H]1O[C@H](COC(=O)c2ccccc2)[C@@H](O[C@@H]2O[C@H](COC(=O)c3ccccc3)[C@H](OC(C)=O)[C@H](O)[C@H]2OC(=O)c2ccccc2)[C@H](O[C@@H]2O[C@@H](C)[C@@H](OCc3ccccc3)[C@@H](OCc3ccccc3)[C@@H]2OCc2ccccc2)[C@H]1OC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 91.3 %

Procedure:
Compound 22 (5 g) was dissolved a 1:1 mixture of benzene and triethylorthoacetate (110 mL), containing 4-toluenesulfonic acid (0.2 g), and the mixture was stirred for 1 h at room temperature. The acid was neutralized with triethylamine, and the mixture evaporated to dryness. The residue was dissolved in 80% aqueous acetic acid (75 mL) and stirred for 40 min at room temperature. The acetic acid was evaporated under diminished pressure and the last traces were removed by co-evaporation with toluene to yield 23 (4.7 g, 91.3%); [α]D, -4.5° (c 0.8, chloroform), t.l.c. (5:1 ethyl acetate-toluene). 13C NMR (CDCl3): δ170.98 (COCH3), 166.75, 166.33, 166.18, 165.07 (4×PhCO), 102.03, 101.08 (C-1, C-1'), 98.16 (C-1 fuc), 80.07, 78.23 (C-3, C-4), 74.69, 73.53, 73.24 (3×PhCH2), 70.66 [OCH2 (CH2)6 ], 63.23, 61.42 (C-6, C-6'), 32.25-23.14 [(CH2)6CH3 ], 21.20 (COCH3), 17.49 (C-6 fuc), and 14.63 (CH3).
Reaction SMILES: [NH3:1].N.N.N.N.N.[OH2:7].O.O.O.[OH:11][Mo:12](O)(=O)=O.[OH:16][Mo](O)(=O)=O.[OH:21][Mo](O)(=O)=O.[O:26]=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.N.N.N.N.N.N.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.[Mo:72].[Mo].[Mo].[Mo].[Mo].[Mo].[Mo].[P]=O.[Mo].[P]>OP(O)(O)=O.O.[NH4+].[NH4+].[O-][Mo]([O-])(=O)=O>[NH3:1].[NH3:1].[NH3:1].[NH3:1].[NH3:1].[NH3:1].[OH2:11].[OH2:16].[OH2:21].[OH2:26].[OH2:7].[OH2:11].[OH2:11].[OH2:11].[OH2:11].[OH2:11].[OH2:11].[OH2:11].[OH2:11].[OH2:11].[OH2:11].[OH2:11].[OH2:11].[OH2:11].[OH2:11].[OH2:11].[OH2:11].[OH2:11].[OH2:11].[OH2:11].[Mo:12].[Mo:12].[Mo:12].[Mo:12].[Mo:12].[Mo:12].[Mo:12].[Mo:72]=[O:7]
Reactant: O=[Mo](=O)(O)O
Reactant: O=[Mo](=O)=O
Agent: O=[Mo](=O)([O-])[O-]
Agent: [Mo]
Agent: N
Solvent: O
Product: O=[Mo]
Reaction time: 6 h

Procedure:
A γ-alumina obtained as {fraction (1/16)} inch extrudates from Criterion Catalyst Company L.P., Michigan City, Ind. was used. First, an ammonium heptamolybdate solution was prepared by dissolving (NH4)6Mo7O24.4H2O in concentrated H3PO4 and water so that the ammonium molybdate concentration was 9.855 weight %, the H3PO4 concentration was 12.681 weight %, and water made up the rest. Then, 10 g of the alumina was impregnated at 25° C. with 5.32 g of the ammonium heptamolybdate solution to form a mixture. The mixture was then calcined in air at 538° C. for 6 hours to produce 10.18 g of a molybdenum oxide- and phosphorus oxide-impregnated alumina containing 2.807 weight % molybdenum and 2.096 weight % phosphorus (control catalyst).
Reaction SMILES: C([O:8][C:9]1[C:10]([F:29])=[C:11]([F:28])[CH:12]=[C:13]2[C:18]=1[N:17]([CH:19]1[CH2:21][CH2:20]1)[CH:16]=[C:15]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:14]2=[O:27])C1C=CC=CC=1.CCO>C1COCC1.[Pd]>[CH:19]1([N:17]2[C:18]3[C:13](=[CH:12][C:11]([F:28])=[C:10]([F:29])[C:9]=3[OH:8])[C:14](=[O:27])[C:15]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:16]2)[CH2:20][CH2:21]1
Reactant: CCOC(=O)c1cn(C2CC2)c2c(OCc3ccccc3)c(F)c(F)cc2c1=O
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CCO
Product: CCOC(=O)c1cn(C2CC2)c2c(O)c(F)c(F)cc2c1=O
Yield: 47.4 %

Procedure:
A solution of ethyl 8-(benzyloxy)-1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate (3.00 g, 7.51 mmol) in THF (60 mL)-EtOH (10 mL) was hydrogenated under atmospheric pressure over 10% Pd/C (300 mg) at room temperature for 2 h. The catalyst was removed by filtration over Celite and the filtrate was concentrated in vacuo. The crude product washed with Hexane and dried to yield ethyl 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-hydroxy-4-oxoquinoline-3-carboxylate (1.10 g, 47%) as a colorless solid.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][OH:8].[C:9]1(=[O:19])[NH:13][C:12](=[O:14])[C:11]2=[CH:15][CH:16]=[CH:17][CH:18]=[C:10]12.[K].C(OCC)(=O)C.O>CN(C)C=O>[OH:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][N:13]1[C:12](=[O:14])[C:11]2=[CH:15][CH:16]=[CH:17][CH:18]=[C:10]2[C:9]1=[O:19]
Reactant: OCCCCCCBr
Reactant: O=C1NC(=O)c2ccccc21
Agent: [K]
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: O=C1c2ccccc2C(=O)N1CCCCCCO
Reaction time: 72 h

Procedure:
6-Bromohexan-1-ol (8 g, 44 mmol) and potassium phthalimide (16.4 g, 88 mmol) were heated at 90° C. for two hours in dry N,N-dimethylformamide (50 ml). The mixture was cooled and partitioned between chloroform (150 ml) and water (150 ml). The organic layer washed with water (2×150 ml), dried over anhydrous magnesium sulphate, filtered, and the filtrate evaporated under reduced pressure to give a yellow liquid. The liquid was left at 4° C. for 72 hours before repartitioning between ethyl acetate (150 ml) and water (150 ml). The organic layer was washed with water (2×150 ml), dried over anhydrous magnesium sulphate, filtered, and the filtrate evaporated under reduced pressure. Diethyl ether was added and following cooling the solid was removed by filtration. The process was repeated and the liquors were evaporated to give N-(6-hydroxyhexyl)-phthalimide. 1H-NMR: (60 MHz) (CDCl3), δ 7.7 (4H,s), 3.6 (5H,m) and 1.4 (8H,m) ppm