Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([NH:20][C@H:21]([CH2:24][CH3:25])[CH:22]=[O:23])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:26]([Mg]Br)[CH3:27].O>CCOCC>[C:1]([NH:20][C@@H:21]([CH2:24][CH3:25])[CH:22]([OH:23])[CH2:26][CH3:27])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC[Mg]Br
Reactant: CC[C@H](C=O)NC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: O
Solvent: CCOCC
Product: CCC(O)[C@H](CC)NC(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: -78 °C
Reaction time: 2 h

Procedure:
To a stirred solution of (R)-2-(trityl-amino)-butyraldehyde (1.5 g, 1 eq, 4.53 mmol) in Et2O (150 mL) under an argon atmosphere at −78° C., was added ethylmagnesium bromide (3 M in Et2O, 1.51 mL, 1 eq, 4.53 mmol) dropwise. The solution was stirred at −78° C. for 2 h, then allowed to warm to room temperature over 16 h. The mixture was recooled to 0° C., H2O (150 mL) added, and the organic phase separated. The aqueous phase was extracted with more Et2O (2×50 mL), and the combined organic phase washed with brine (50 mL), dried (MgSO4) and evaporated in vacuo. The residue was purified by silica gel column chromatography, eluted with hexane:ether (90:10) to afford the title compound as a light yellow oil. Yield: 1.19 g (73%). (65% de 3R,4S: 35% de 3S,4S). 1H-NMR (d6-DMSO, 250 MHz): δ 0.46+0.69 (t & m, 6H, J=7.34 Hz, —NHCH(CH2CH3)CH(CH2CH3)OH), 1.13-1.29 (m, 4H, —NHCH(CH2CH3) CH(CH2CH3)OH), 2.17 (m, 1H, —NHCH(CH2CH3)CH(CH2CH3)OH), 2.55 (m, 1H, —NHCH(CH2CH3)CH(CH2CH3)OH), 3.20-3.39 (m, 1H, —NHCH(CH2CH3)CHCH2CH3)OH), 4.29 & 4.39 (2×d, 1H, J=4.74 & 5.53 Hz, —NHCH(CH2CH3)CH(CH2CH3)OH), 7.15-7.52 (m, 15H, 3×Ph).
Reaction SMILES: [F:1][C:2]([F:15])=[CH:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]([CH3:14])=[O:13].[CH3:16][Mg]Br.Cl>C(OCC)C>[F:1][C:2]([F:15])=[CH:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]([CH3:16])([OH:13])[CH3:14]
Reactant: CC(=O)CCCCCCCCC=C(F)F
Reactant: C[Mg]Br
Agent: Cl
Solvent: CCOCC
Product: CC(C)(O)CCCCCCCCC=C(F)F
Temperature: 25 °C
Reaction time: 18 h
Yield: 52.2 %

Procedure:
Under a nitrogen atmosphere, a stirred solution of 2.0 grams (0.009 mole) of methyl 10,10-difluoro-9-decenyl ketone in 25 ml of diethyl ether was cooled to 0° C., and 2.96 ml (0.009 mole) of methylmagnesium bromide (3.1 Molar solution) was added via syringe. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature. Analysis of the reaction mixture by gas chromatography indicated that the reaction had stopped at approximately 50% of completion. An additional 3.0 ml of methylmagnesium bromide was added via syringe, and the reaction mixture was allowed to stir for 18 hours. After this time the reaction mixture was poured into 20 ml of ice containing 5 ml of an aqueous 10% hydrochloride acid solution. The aqueous layer was separated and washed with three 10 ml portions of diethyl ether. The extracts were combined with the organic layer, and the combination was washed with three 10 ml portions of water. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residual oil. The oil was subjected to column chromatography on silica gel. Elution was accomplished with methylene chloride and then with methanol. The appropriate fractions were combined and concentrated under reduced pressure yielding 1.1 grams of 12,12-difluoro-2-methyl-11-dodecen-2-ol. The nmr spectrum was consistent with the proposed structure.
Reaction SMILES: [C:1]([O:4][CH2:5][C:6]1[N:7]([CH2:28][C:29]([OH:32])([CH3:31])[CH3:30])[C:8]2[C:17]3[CH:16]=[CH:15][C:14]([O:18][CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)=[CH:13][C:12]=3[N+:11]([O-])=[CH:10][C:9]=2[N:27]=1)(=[O:3])[CH3:2].[OH-].[NH4+:34].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>ClCCl>[C:1]([O:4][CH2:5][C:6]1[N:7]([CH2:28][C:29]([OH:32])([CH3:31])[CH3:30])[C:8]2[C:17]3[CH:16]=[CH:15][C:14]([O:18][CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)=[CH:13][C:12]=3[N:11]=[C:10]([NH2:34])[C:9]=2[N:27]=1)(=[O:3])[CH3:2]
Reactant: [NH4+]
Reactant: CC(=O)OCc1nc2c[n+]([O-])c3cc(OCc4ccccc4)ccc3c2n1CC(C)(C)O
Agent: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: [OH-]
Solvent: ClCCl
Product: CC(=O)OCc1nc2c(N)nc3cc(OCc4ccccc4)ccc3c2n1CC(C)(C)O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of [7-benzyloxy-1-(2-hydroxy-2-methylpropyl)-5-oxido-1H-imidazo[4,5-c]quinolin-2-yl]methyl acetate (40.0 g, 0.0918 mol) in dichloromethane (650 mL) was cooled to 0° C.; ammonium hydroxide (250 mL of 28%) was added. A solution of p-toluenesulfonyl chloride (29.1 g, 0.153 mol) in dichloromethane (200 mL) was added over a period of 12 minutes while maintaining the reaction temperature below 5.5° C. The reaction mixture was then allowed to warm to room temperature and stirred for one hour. The reaction mixture was diluted with dichloromethane (100 mL), and the organic layer was washed with deionized water (2×400 mL), dried over magnesium sulfate, and filtered. The solution was then treated with activated charcoal for one hour, filtered through a layer of CELITE filter aid, concentrated under reduced pressure, and further dried under vacuum at 60° C. to provide 40.1 g of [4-amino-7-benzyloxy-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-2-yl]methyl acetate.
Reaction SMILES: [CH3:1][C:2]1[N:7]2[N:8]=[C:9]([CH2:11][P+](C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[N:10]=[C:6]2[C:5]([CH3:31])=[N:4][CH:3]=1.[Cl-].[CH:33]([C:35]1[CH:44]=[CH:43][C:42]2[C:37](=[CH:38][CH:39]=[C:40]([C:45]#[N:46])[CH:41]=2)[N:36]=1)=O.O1CCCC1.N12CCCN=C1CCCCC2>>[CH3:1][C:2]1[N:7]2[N:8]=[C:9](/[CH:11]=[CH:33]/[C:35]3[CH:44]=[CH:43][C:42]4[C:37](=[CH:38][CH:39]=[C:40]([C:45]#[N:46])[CH:41]=4)[N:36]=3)[N:10]=[C:6]2[C:5]([CH3:31])=[N:4][CH:3]=1
Reactant: Cc1ncc(C)n2nc(C[P+](c3ccccc3)(c3ccccc3)c3ccccc3)nc12
Reactant: N#Cc1ccc2nc(C=O)ccc2c1
Agent: [Cl-]
Solvent: C1CCC2=NCCCN2CC1
Solvent: C1CCOC1
Product: Cc1ncc(C)n2nc(/C=C/c3ccc4cc(C#N)ccc4n3)nc12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a suspension of (5,8-Dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-ylmethyl)-triphenyl-phosphonium; chloride (0.222 g, 0.483 mmol) and 2-Formyl-quinoline-6-carbonitrile (80 mg, 0.4 mmol) in dry Tetrahydrofuran (6 mL, 80 mmol) was added 1,8-Diazabicyclo[5.4.0]undec-7-ene (66 uL, 0.44 mmol) (reaction mixture turns slightly yellow for a while and precipitation changes character) and the mixture was stirred at room temperature under an atmosphere of Argon overnight. The mixture was rotovaped and the THF was evaporated off. The solid was dissolved in DCM and was chromatographed on silicagel (0-30% MeOH in EtOAc). Pure product 2-[(E)-2-(5,8-Dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)-vinyl]-quinoline-6-carbonitrile precipitates in one of the fractions (10): isolated by filtration. Yield: 6 mg white solid.
Reaction SMILES: [CH3:1]OC([C@@H]1C[C@@H](O)CCN1C(OC(C)(C)C)=O)=O.[CH3:19][O:20][C:21]([C@@H:23]1[CH2:27][C@H:26]([NH2:28])[CH2:25][N:24]1[CH2:29][CH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1)=[O:22]>>[CH3:19][O:20][C:21]([C@@H:23]1[CH2:27][C@H:26]([NH2:28])[CH2:25][CH2:1][N:24]1[CH2:29][CH:30]1[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]1)=[O:22]
Reactant: COC(=O)[C@@H]1C[C@@H](O)CCN1C(=O)OC(C)(C)C
Reactant: COC(=O)[C@@H]1C[C@H](N)CN1CC1CCCCC1
Product: COC(=O)[C@@H]1C[C@H](N)CCN1CC1CCCCC1

Procedure:
(2S,4R)-4-amino-1-cyclohexylmethyl-piperidine-2-carboxylic acid methyl ester was prepared from (2S,4S)-4-hydroxy-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester in a similar reaction sequence used in the preparation of (2S,4S)-4-amino-1-cyclohexylmethyl-pyrrolidine-2-carboxylic acid methyl ester. MS caled. for C14H27N2O2 [(M+H)+] 255, obsd. 255.
Reaction SMILES: Cl.[Br:2][C:3]1[N:4]=[C:5]([CH2:11]Cl)[N:6]([CH2:9][CH3:10])[C:7]=1[CH3:8].C([O-])([O-])=O.[K+].[K+].[F:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([C:26]2[NH:27][CH:28]=[CH:29][N:30]=2)[N:21]=1.O>CN(C=O)C>[Br:2][C:3]1[N:4]=[C:5]([CH2:11][N:30]2[CH:29]=[CH:28][N:27]=[C:26]2[C:22]2[CH:23]=[CH:24][CH:25]=[C:20]([F:19])[N:21]=2)[N:6]([CH2:9][CH3:10])[C:7]=1[CH3:8]
Reactant: CCn1c(CCl)nc(Br)c1C
Reactant: Fc1cccc(-c2ncc[nH]2)n1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCn1c(Cn2ccnc2-c2cccc(F)n2)nc(Br)c1C
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a solution of 77 mg (0.27 mmol) of 4-bromo-2-chloromethyl-1-ethyl-5-methyl-1H-imidazole hydrochloride in 1.5 ml of DMF is added 224 mg (1.62 mmol) of K2CO3 and 45 mg (0.27 mmol) of 2-fluoro-6-(1H-imidazol-2-yl)-pyridine. The mixture is stirred at room temperature for 24 hours. 5 ml water is added and the mixture was extracted with EtOAc (3×15 ml). The combined extracts are washed with 15 ml brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue is purified by preparative TLC, developing with 10:0.4:0.05 CH2Cl2—MeOH—NH4OH solution. The purified compound is then dissolved in 3 ml of EtOAc and to it is added 2 ml of 2N HCl in ether. The resulting suspension is stirred at room temperature for 15 minutes. Evaporation of the solvent 5 provides the title compound as a white powder. LC-MS (M+1) 364.
Reaction SMILES: Br[C:2]1[C:10]2[C:5](=[CH:6][C:7]([S:11]([N:14]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][C:22]=3[O:29][CH3:30])[C:15]3[S:19][N:18]=[CH:17][N:16]=3)(=[O:13])=[O:12])=[CH:8][CH:9]=2)[NH:4][CH:3]=1.[CH3:31][N:32]1[C:36]([C:37]2[CH:42]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:40]=[CH:39][C:38]=2B(O)O)=[CH:35][CH:34]=[N:33]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[CH3:30][O:29][C:22]1[CH:23]=[C:24]([O:27][CH3:28])[CH:25]=[CH:26][C:21]=1[CH2:20][N:14]([C:15]1[S:19][N:18]=[CH:17][N:16]=1)[S:11]([C:7]1[CH:6]=[C:5]2[C:10]([C:2]([C:38]3[CH:39]=[CH:40][C:41]([C:43]([F:46])([F:44])[F:45])=[CH:42][C:37]=3[C:36]3[N:32]([CH3:31])[N:33]=[CH:34][CH:35]=3)=[CH:3][NH:4]2)=[CH:9][CH:8]=1)(=[O:12])=[O:13]
Reactant: Cn1nccc1-c1cc(C(F)(F)F)ccc1B(O)O
Reactant: COc1ccc(CN(c2ncns2)S(=O)(=O)c2ccc3c(Br)c[nH]c3c2)c(OC)c1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: COc1ccc(CN(c2ncns2)S(=O)(=O)c2ccc3c(-c4ccc(C(F)(F)F)cc4-c4ccnn4C)c[nH]c3c2)c(OC)c1
Temperature: 90 °C
Yield: 80.5 %

Procedure:
A vial was charged with 3-bromo-N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (324 mg, 0.636 mmol), (2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)boronic acid (Intermediate G) (223 mg, 0.827 mmol), potassium phosphate (405 mg, 1.908 mmol), and Pd(AmPhos)2Cl2 (22.52 mg, 0.032 mmol), 1,4-dioxane (2.4 mL), and water (0.8 mL). The vial was flushed with Ar, sealed, and heated in a microwave reactor to 90° C. for 40 min. The reaction mixture was diluted with water and extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by chromatography on silica gel (50 to 100% EtOAc/Heptane) to afford N-(2,4-dimethoxybenzyl)-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (335.1 mg, 0.512 mmol, 80% yield) as a yellow foam that was about 90% pure as assessed by NMR. 1H NMR (400 MHz, DMSO-d6) δ=11.92 (d, J=2.4 Hz, 1 H), 8.34 (s, 1 H), 8.00 (dd, J=0.4, 1.8 Hz, 1 H), 7.95-7.87 (m, 2 H), 7.79-7.76 (m, 1 H), 7.71 (d, J=8.6 Hz, 1 H), 7.49 (dd, J=1.9, 8.6 Hz, 1 H), 7.41 (d, J=1.9 Hz, 1 H), 7.20 (d, J=2.7 Hz, 1 H), 6.92 (d, J=8.4 Hz, 1 H), 6.45 (d, J=2.4 Hz, 1 H), 6.40-6.34 (m, 2H), 5.09 (s, 2 H), 3.72 (s, 3 H), 3.68 (s, 3 H), 3.19 (s, 3 H). m/z (ESI) 655.2 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:8]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=2[OH:18])=O)=[N:4][CH:5]=[CH:6][N:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1C=CC=CC=1.ClC(Cl)(Cl)C#N>C(OCC)(=O)C.CO>[F:17][C:14]1[CH:15]=[CH:16][C:11]2[N:10]=[C:8]([C:3]3[C:2]([NH2:1])=[N:7][CH:6]=[CH:5][N:4]=3)[O:18][C:12]=2[CH:13]=1
Reactant: Nc1nccnc1C(=O)Nc1ccc(F)cc1O
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Solvent: N#CC(Cl)(Cl)Cl
Product: Nc1nccnc1-c1nc2ccc(F)cc2o1
Temperature: -10 °C
Yield: 20.2 %

Procedure:
3-amino-N-(4-fluoro-2-hydroxy-phenyl)pyrazine-2-carboxamide (1.6 g) and triphenylphosphine (5.07 g) were dissolved into pyridine (20 ml). The mixture was cooled to −10° C. in a ice-salt bath. Then, 2,2,2-trichloroacetonitrile (2.79 g) was added slowly. The resulting mixture was heated to reflux for 12 hours. The resulting mixture was diluted with ethyl acetate/methanol (4/1, 100 ml). The mixture was filtered by celite (diatomaceous earth), and the mixture was washed with 1M HCl. The organic layer was concentrated and the residue was purified by chromatography on silica gel (hexane/ethyl acetate/Methanol) to yield 3-(6-fluoro-1,3-benzoxazol-2-yl)pyrazin-2-amine (0.3 g). NMR Spectrum: (400 MHz, DMSOd6) 8.23 (s, 1H), 8.00 (s, 1H), 7.85 (m, 1H), 7.80 (m, 4H), 7.30 (m, 1H); Mass spectrum: M+H+ 231.
Reaction SMILES: [CH2:1]([O:3][CH2:4][CH2:5][C:6]([OH:24])([CH3:23])[CH:7]=[CH:8][CH:9]1[CH2:13][CH2:12][C:11](=[O:14])[CH:10]1[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][OH:22])[CH3:2].[C:25](OC(=O)C)(=[O:27])[CH3:26]>N1C=CC=CC=1.O>[C:25]([O:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH:10]1[CH:9]([CH:8]=[CH:7][C:6]([OH:24])([CH3:23])[CH2:5][CH2:4][O:3][CH2:1][CH3:2])[CH2:13][CH2:12][C:11]1=[O:14])(=[O:27])[CH3:26]
Reactant: CCOCCC(C)(O)C=CC1CCC(=O)C1CCCCCCCO
Reactant: CC(=O)OC(C)=O
Solvent: O
Solvent: c1ccncc1
Product: CCOCCC(C)(O)C=CC1CCC(=O)C1CCCCCCCOC(C)=O
Reaction time: 72 h

Procedure:
A solution of 7-[2-(5-ethoxy-3-hydroxy-3-methylpent-1-enyl)-5-oxocyclopentyl]heptanol [0.4 g; prepared as hereinbefore described in Example 7(iv)] in dry pyridine (4 ml.) was treated with acetic anhydride (4 ml.) and the resulting solution was allowed to stand at ambient temperature for 3 days and then diluted with water (100 ml.) with external cooling by means of an ice-bath. The resulting aqueous solution was extracted three times with chloroform, and the combined extracts were dried over sodium sulphate. Evaporation in vacuo gave a crude product which was purified by preparative thin layer chromatrography on silica gel using a mixture of toluene, dioxan and acetic acid (65:15:1 by volume) as eluant, to give 2-(7-acetoxyheptyl)-3-(5-ethoxy-3-hydroxy-3-methylpent-1-enyl)cyclopentanone (0.17 g.). Elemental analysis: Found: C, 68.7; H, 10.3%; C22H38O5 requires C, 69.1; H, 10.0%. N.M.R. (approximately 10% w/v solution in deuterochloroform): multiplets at 1.0-1.9δ, 1.9-2.9δ, singlet at 2.05δ, multiplet at 3.35δ, triplet at 4.05δ, (J=6.5 cycles/second), multiplet at 5.6δ.
Reaction SMILES: [CH:1]([C:7]1[NH:8][C:9]2[C:14]([CH:15]=1)=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:2][CH2:3][CH2:4][CH2:5][CH3:6]>C(O)C.[Pd]>[CH2:1]([C:7]1[NH:8][C:9]2[C:14]([CH:15]=1)=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCC=Cc1cc2ccccc2[nH]1
Agent: [Pd]
Solvent: CCO
Product: CCCCCCc1cc2ccccc2[nH]1

Procedure:
2-hex-1-enyl-1H-indole was dissolved in ethanol and 10% palladium on carbon was added to the solution. The reaction flask was sealed and exposed to hydrogen gas under pressure until the hydrogen gas consumption was stopped completely. The reaction mixture was filtered through Celite. The solvent was evaporated to afford the product.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:35]=[CH:36][CH:37]=1)[CH2:7][N:8]1[C:12](=[O:13])[C:11]2([CH2:18][CH2:17][N:16]([C:19]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[O:20])[CH2:15][CH2:14]2)[N:10]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:9]1)([O-])=O.[Cl-].[NH4+]>[Fe].C(O)C.O>[NH2:1][C:4]1[CH:5]=[C:6]([CH:35]=[CH:36][CH:37]=1)[CH2:7][N:8]1[C:12](=[O:13])[C:11]2([CH2:18][CH2:17][N:16]([C:19]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[O:20])[CH2:15][CH2:14]2)[N:10]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH2:9]1
Reactant: O=C(OCc1ccccc1)N1CCC2(CC1)C(=O)N(Cc1cccc([N+](=O)[O-])c1)CN2c1ccccc1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: Nc1cccc(CN2CN(c3ccccc3)C3(CCN(C(=O)OCc4ccccc4)CC3)C2=O)c1
Yield: 111.1 %

Procedure:
To a refluxing solution of benzyl 3-(3-nitrobenzyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylate (0.77 g, 1.53 mmol) and ammonium chloride (0.96 g, 18.0 mmol) in 2:1 mixture of ethanol/water (18 mL), was added iron powder (0.3 g, 5.4 mmol) over a period of 45 minutes. After refluxing for another hour, the reaction mixture was extracted with dichloromethane, washed the organic extracts with water and brine. The organic phase was dried over MgSO4 and concentrated to obtain benzyl 3-(3-aminobenzyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylate (0.80 g, 95%).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:25])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[NH:13][CH:12]=2)=[C:6]([O:23][CH3:24])[CH:5]=1.[F:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]=[C:34]=[O:35])=[CH:29][CH:28]=1>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH3:1][O:2][C:3](=[O:25])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[CH:18]=3)[N:13]([C:34](=[O:35])[NH:33][C:30]3[CH:31]=[CH:32][C:27]([F:26])=[CH:28][CH:29]=3)[CH:12]=2)=[C:6]([O:23][CH3:24])[CH:5]=1
Reactant: COC(=O)c1ccc(Cc2c[nH]c3ccc([N+](=O)[O-])cc23)c(OC)c1
Reactant: O=C=Nc1ccc(F)cc1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: COC(=O)c1ccc(Cc2cn(C(=O)Nc3ccc(F)cc3)c3ccc([N+](=O)[O-])cc23)c(OC)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 87.7 %

Procedure:
To a stirred solution of 4-[5-nitro-1H-indol-3-ylmethyl]-3-methoxy-benzoic acid methylester (1.30 grams, 3.82 mmol) and 4-dimethylaminopyridine (0.58 mL, 4.77 mmol) in methylene chloride (60 mL) was added 4-fluorophenylisocyanate (0.70 mL, 5.73 mmol). The resulting solution was stirred for 18 hours, at room temperature, and then diluted with methylene chloride. The solution was washed with 1 M hydrochloric acid, water and brine, then dried over magnesium sulfate. Concentration in vacuo followed by trituration in diethylether gave 4-[1-(4-fluoro-phenylcarbamoyl)-5-nitro-1H-indol-3-ylmethyl]-3-methoxy-benzoic acid methylester (1.60 grams, 88% yield).
Reaction SMILES: [CH:1]([NH2:5])([CH2:3][CH3:4])[CH3:2].Br[CH:7]([CH2:22][CH3:23])[C:8]([C:10]1[CH:19]=[CH:18][C:17]([OH:20])=[C:16]2[C:11]=1[CH:12]=[CH:13][C:14](=[O:21])[NH:15]2)=[O:9]>CO>[CH:1]([NH:5][CH:7]([CH2:22][CH3:23])[C:8]([C:10]1[CH:19]=[CH:18][C:17]([OH:20])=[C:16]2[C:11]=1[CH:12]=[CH:13][C:14](=[O:21])[NH:15]2)=[O:9])([CH2:3][CH3:4])[CH3:2]
Reactant: CCC(C)N
Reactant: CCC(Br)C(=O)c1ccc(O)c2[nH]c(=O)ccc12
Solvent: CO
Product: CCC(C)NC(CC)C(=O)c1ccc(O)c2[nH]c(=O)ccc12

Procedure:
10 ml of iso-propylamine (III) and 50 ml of methanol were added to 5 g of the 5-(α-bromobutyryl)-8-hydroxycarbostyril (IV) obtained in Examples 1 to 3. The resulting mixture was heated under refluxing for 6 hours followed by concentration to dryness. The reaction product was further worked up in the same manner as described in Example 1 to obtain 4.2 g of a methanol solvate of 5-(α-iso-propylaminobutyryl)-8-hydroxycarbostyril (II) having a melting point of 136°-137° C (with foaming and decomposition).