Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[NH:6][C:7]3[C:8]([CH3:13])=[CH:9][CH:10]=[CH:11][C:12]=3[C:4]=2[CH2:3]1.[OH-].[K+].[F:18][C:19]([F:29])([F:28])[C:20]1[CH:25]=[CH:24][C:23]([CH:26]=[CH2:27])=[CH:22][N:21]=1.N1C2C(=CC=CC=2)C=C1.C(O)(C(F)(F)F)=O>CN1C(=O)CCC1.O>[F:29][C:19]([F:18])([F:28])[C:20]1[N:21]=[CH:22][C:23]([CH2:26][CH2:27][N:6]2[C:7]3[C:8]([CH3:13])=[CH:9][CH:10]=[CH:11][C:12]=3[C:4]3[CH2:3][N:2]([CH3:1])[CH2:15][CH2:14][C:5]2=3)=[CH:24][CH:25]=1
Reactant: Cc1cccc2c3c([nH]c12)CCN(C)C3
Reactant: C=Cc1ccc(C(F)(F)F)nc1
Agent: [K+]
Agent: [OH-]
Agent: c1ccc2[nH]ccc2c1
Solvent: O=C(O)C(F)(F)F
Solvent: CN1CCCC1=O
Solvent: O
Product: Cc1cccc2c3c(n(CCc4ccc(C(F)(F)F)nc4)c12)CCN(C)C3
Reaction time: 0.17 h

Procedure:
To a solution of 2,3,4,5-tetrahydro-2,6-dimethyl-1H-pyrido[4,3-b]indole (200 mg, 1.0 mmol) in NMP (2.5 ml), powdered KOH (561 mg, 10 mmol) was added and stirred for 10 min at 25 deg C. After which 2-(trifluoromethyl)-5-vinylpyridine (346 mg, 2.0 mmol) was added slowly to the above solution and stirred for 16 h at 25 deg C. After completion of the reaction (monitored by LCMS), water (5 mL) was added to the crude, and extracted with the ethyl acetate. The organic layer was dried and concentrated. The resulting crude was purified by reverse-phase chromatography (C-18, 500 mm×50 mm, Mobile Phase A=0.05% TFA in water, B=0.05% TFA in acetonitrile, Gradient: 10% B to 80% B in 30 min, injection vol. 5 mL) to obtain 40 mg (8.2%) of 5-(2-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-2,3,4,5-tetrahydro-2,6-dimethyl-1H-pyrido[4; 3-b]indole as TFA salt.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:38]2[CH2:42][C@H:41]([CH2:43][NH:44][C:45](=[O:47])[CH3:46])[O:40][C:39]2=[O:48])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:37])[CH2:15][O:16][C:17]2[CH:22]=[CH:21][C:20]([CH2:23][O:24][CH:25]3[CH2:30][O:29][C:28]4=[N:31][C:32]([N+:34]([O-:36])=[O:35])=[CH:33][N:27]4[CH2:26]3)=[CH:19][CH:18]=2)[CH2:10][CH2:9]1.C(OC(=O)COC1C=CC(CO[C@@H]2COC3=NC([N+]([O-])=O)=CN3C2)=CC=1)(C)(C)C.FC1C=C(N2CC(CNC(=O)C)OC2=O)C=CC=1N1CCNCC1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C>C(O)(C(F)(F)F)=O.C(Cl)Cl.C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([N:38]2[CH2:42][C@H:41]([CH2:43][NH:44][C:45](=[O:47])[CH3:46])[O:40][C:39]2=[O:48])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:9][CH2:10][N:11]([C:14](=[O:37])[CH2:15][O:16][C:17]2[CH:18]=[CH:19][C:20]([CH2:23][O:24][C@@H:25]3[CH2:30][O:29][C:28]4=[N:31][C:32]([N+:34]([O-:36])=[O:35])=[CH:33][N:27]4[CH2:26]3)=[CH:21][CH:22]=2)[CH2:12][CH2:13]1
Reactant: CC(=O)NC[C@H]1CN(c2ccc(N3CCN(C(=O)COc4ccc(COC5COc6nc([N+](=O)[O-])cn6C5)cc4)CC3)c(F)c2)C(=O)O1
Agent: CC(=O)NCC1CN(c2ccc(N3CCNCC3)c(F)c2)C(=O)O1
Agent: CC(C)(C)OC(=O)COc1ccc(CO[C@@H]2COc3nc([N+](=O)[O-])cn3C2)cc1
Agent: CCN=C=NCCCN(C)C
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: O=C(O)C(F)(F)F
Product: CC(=O)NC[C@H]1CN(c2ccc(N3CCN(C(=O)COc4ccc(CO[C@@H]5COc6nc([N+](=O)[O-])cn6C5)cc4)CC3)c(F)c2)C(=O)O1
Temperature: 25 °C
Reaction time: 24 h
Yield: 4 %

Procedure:
(S)—N-{3-[3-Fluoro-4-(4-{2-[4-(2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-yloxymethyl)-phenoxy]-acetyl}-piperazin-1-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide. A solution of [4-(2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6(S)-yloxylmethyl)-phenoxy]-acetic acid tert-butyl ester (100 mg, 0.25 mmol) in TFA/CH2Cl2 (2 mL) was stirred at room temperature for 2 h. The resultant mixture was concentrated in vacuo, and diluted with DCM, to the solution was added N-[3-(3-fluoro-4-piperazin-1-yl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide (50 mg, 0.15 mmol) (prepared by following the procedure disclosed by U.S. Pat. No. 5,547,950 or Brickner 1996), HOBt (21.6 mg, 0.16 mmol), EDCI (30.7 mg, 0.16 mmol) and DIPEA (0.20 ml). The mixture was stirred at room temperature for 24 hours diluted with DCM, washed with sat. NaHCO3, 1 N HCl and sat. NaHCO3, dried over sodium sulfate, and concentrated in vacuo. The crude product was purified by preparative TLC plates (5% MeOH in dichloromethane) to give the title product as a solid (6.0 mg, 4%). ESI MS m/z 668.4 (M+H+).
Reaction SMILES: CS(C)=O.C(Cl)(=O)C(Cl)=O.[CH2:11]([Si:13]([CH2:25][CH3:26])([CH2:23][CH3:24])[C:14]1[O:15][CH:16]=[C:17]([CH2:19][CH2:20][CH2:21][OH:22])[CH:18]=1)[CH3:12].C(N(CC)CC)C>ClCCl>[CH2:25]([Si:13]([CH2:11][CH3:12])([CH2:23][CH3:24])[C:14]1[O:15][CH:16]=[C:17]([CH2:19][CH2:20][CH:21]=[O:22])[CH:18]=1)[CH3:26]
Reactant: CC[Si](CC)(CC)c1cc(CCCO)co1
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CS(C)=O
Product: CC[Si](CC)(CC)c1cc(CCC=O)co1
Reaction time: 0.08 h

Procedure:
A mixture of dimethyl sulfoxide (0.9 ml) and dichloromethane (9 ml) was added to a solution of oxalyl chloride (0.64 ml, 7.39 mmol) at -78 degrees under argon. After 5 minutes, a solution of 3-(2-triethylsilyl-4-furyl)propan-1-ol (1.27 g, 5.28 mmol) in dichloromethane (9.0 ml) was added dropwise and after 20 minutes, triethylamine (2.9 ml, 21.1 mmol) was added. Stirring was continued at -78 degrees C. for 40 minutes and at room temperature for 3 hours. The mixture was quenched with water and was extracted thoroughly with ethyl ether. Evaporation of the dried (magnesium sulfate) extracts gave an oil, which was purified by a silica column to give the titled aldehyde.
Reaction SMILES: [C:1]([C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:11]=2)[C:6]([OH:20])=[C:5]([C:21](OC)=[O:22])[N:4]=1)#[N:2].[NH2:25][CH2:26][CH2:27][C@H:28]([OH:32])[C:29]([OH:31])=[O:30].C[O-].[Na+]>COCCO>[C:1]([C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH:11]=2)[C:6]([OH:20])=[C:5]([C:21]([NH:25][CH2:26][CH2:27][C@H:28]([OH:32])[C:29]([OH:31])=[O:30])=[O:22])[N:4]=1)#[N:2]
Reactant: NCC[C@H](O)C(=O)O
Reactant: COC(=O)c1nc(C#N)c2cc(Oc3ccccc3)ccc2c1O
Agent: C[O-]
Agent: [Na+]
Solvent: COCCO
Product: N#Cc1nc(C(=O)NCC[C@H](O)C(=O)O)c(O)c2ccc(Oc3ccccc3)cc12
Temperature: 25 °C

Procedure:
Methyl 1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate (200 mg, 0.63 mmol), (S)-4-amino-2-hydroxybutanoic acid (372 mg, 3.13 mmol, Sigma-Aldrich) and sodium methoxide (155 mg, 2.87 mmol) were suspended in 2-methoxyethanol (7 mL). The resulting mixture was heated to reflux for 3 hours and then cooled to room temperature. The solvent was removed in vacuo and the residue was dissolved in H2O (20 mL) and EtOAc (20 mL). To the stirred mixture was added 1 N hydrochloric acid until pH was 1. The layers were separated and the aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over MgSO4, concentrated, and purified by flash chromatography (0-20% MeOH/CH2Cl2 with 0.5% formic acid) to give the title compound in 180 mg. MS: (−) m/z 406.28 (M−1).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:16]([CH2:17][C:18]([OH:20])=O)[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:33][CH2:34][CH2:35][N:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:16]([CH2:17][C:18]([NH:33][CH2:34][CH2:35][N:36]3[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]3)=[O:20])[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: NCCN1CCCCC1
Reactant: O=C(O)Cn1c(-c2cccc(Cl)c2)nc2cccnc21
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: O=C(Cn1c(-c2cccc(Cl)c2)nc2cccnc21)NCCN1CCCCC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 2-(3-chlorophenyl)-3H-imidazo[4,5-b]pyridine-3-acetic acid (5.4 g, 0.0188 mole), 1,1'-carbonyldiimidazole (3.0 g, 0.0188 mole) in anhydrous tetrahydrofuran (150 ml) was stirred at room temperature with a stream of nitrogen bubbling through it for 21/2 hours. The nitrogen flow was stopped and a solution of 1-(2-aminoethyl)piperidine (2.4 g, 0.0188 mole) in dry tetrahydrofuran (50 ml) was added. The solution was stirred at room temperature under nitrogen for 2 hours. The reaction mixture was concentrated in vacuo and the residue partitioned between methylene chloride (75 ml) in water (75 ml). The layers were separated and the aqueous portion washed with methylene chloride (25 ml). The organic layers were combined and washed with potassium bicarbonate solution (2×50 ml), water (25 ml), dried over sodium sulfate, and concentrated in vacuo. The residue (6.6 g) was recrystallized from isopropyl alcohol-isopropyl ether to give 3.5 g (47%). Recrystallization from isopropyl alcohol-isopropyl ether gave 2.5 g of cream colored solid, mp 114°-115° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([NH2:9])[C:5]([Cl:8])=[N:6][CH:7]=1.C1COCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH:25]1([S:31](Cl)(=[O:33])=[O:32])[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1>C(Cl)Cl.O>[Br:1][C:2]1[CH:3]=[C:4]([NH:9][S:31]([CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)(=[O:33])=[O:32])[C:5]([Cl:8])=[N:6][CH:7]=1
Reactant: O=S(=O)(Cl)C1CCCCC1
Reactant: Nc1cc(Br)cnc1Cl
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Solvent: ClCCl
Product: O=S(=O)(Nc1cc(Br)cnc1Cl)C1CCCCC1
Reaction time: 0.08 h

Procedure:
To a 50 ml round-bottom flask equipped with a stir bar, was added 5-bromo-2-chloropyridin-3-amine (0.250 g, 1 mmol) while under inert atmosphere. The solid was dissolved in THF (10 ml, 122 mmol), then sodium bis(trimethylsilyl)amide (0.650 g, 3 mmol) was added to the mixture and allowed to stir 5 minutes. Then cyclohexanesulfonyl chloride (0.5 ml, 4 mmol) was added into the mixture. The mixture was allowed to stir overnight, while under inert atmosphere. The progress of the reaction was monitored by LC/MS, which showed product and a small amount of bis-sulfone material in the mixture. The mixture was diluted with DCM and water. The organic layer was extracted with DCM (3×25 ml). Combined organics, dried over sodium sulfate, filtered and concentrated in vacuo. The crude was dissolved in methanol (5 ml), then potassium carbonate (0.250 g) was added to the mixture with stirring. After 20 minutes, the progress of the de-sulfonylation reaction was monitored by LC/MS, which showed mostly desired product. The mixture was filtered and concentrated in vacuo. The crude was purified by ISCO silica-gel chromatography, in a gradient of 1-15% ethyl acetate/hexanes. This gave N-(5-bromo-2-chloropyridin-3-yl)cyclohexanesulfonamide (0.140 g, 33% yield) as an off-white amorphous solid. MS (ESI pos. ion) m/z: 354 (MH+). Calc'd exact mass for C11H14BrClN2O2S: 353. 1H NMR (400 MHz, chloroform-d): 1.15-1.35 (m, 2H), 1.52-1.66 (m, 1H), 1.70 (d, J=4.52 Hz, 1H), 1.73 (s, 1H), 1.76-1.86 (m, 1H), 1.92 (d, J=11.54 Hz, 1H), 2.11-2.22 (m, 2H), 2.96-3.05 (m, 1H), 6.70 (s, 1H), 8.15-8.22 (m, 2H).
Reaction SMILES: N#N.[C:3]([C:5]1[CH:19]=[CH:18][C:8]2[N:9]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[N:10]=[N:11][C:7]=2[CH:6]=1)#[CH:4].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.I[CH2:31][CH3:32]>C1COCC1>[C:3]([C:5]1[CH:19]=[CH:18][C:8]2[N:9]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[N:10]=[N:11][C:7]=2[CH:6]=1)#[C:4][CH2:31][CH3:32]
Reactant: C#Cc1ccc2c(c1)nnn2C1CCCCO1
Reactant: CCI
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: N#N
Agent: [Li+]
Solvent: C1CCOC1
Product: CCC#Cc1ccc2c(c1)nnn2C1CCCCO1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A 200-mL round-bottom flask equipped with a magnetic stir bar, a rubber septum and N2 inlet was charged with 5-ethynyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d][1,2,3]triazole (2.5 g, 11 mmol) and anhydrous THF (110 mL). This solution was then cooled down to 0° C. in an ice bath. Then, a solution of LiHMDS (27 mL, 1M THF, 27 mmol) was added dropwise over 15 minutes. The resulting mixture was stirred for 1 h at 0° C. To this mixture at 0° C., iodoethane (4.4 mL, 55 mmol) was added dropwise over 5 minutes. The mixture was gradually warmed to room temperature, stirred for 1 h, and then heated at reflux overnight. The reaction was monitored by LCMS. Upon completion, the reaction mixture was cooled down to room temperature, quenched with water (100 mL), and extracted with ethyl acetate (2×100 mL). The combined organics were washed with water (100 mL), washed with brine (50 mL), dried over sodium sulfate, filtered, and concentrated to give the crude product. This crude material was purified on a silica gel column eluted with 5% ethyl acetate in hexanes affording the title compound as a pale yellow oil (1.6 g). 1H NMR (300 MHz, DMSO-d6): δ 7.92 (s, 1H), 7.85 (dd, 1H), 7.33 (dd, 1H), 6.01 (dd, 1H), 3.86-3.80 (m, 1H), 3.75-3.64 (m, 1H), 2.45-2.36 (m, 3H), 2.08-1.91 (m, 2H), 1.74-1.62 (m, 1H), 1.58-1.50 (m, 2H), 1.11 (t, 3H); LCMS: 172 [(M-THP+H)+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]([O:24][CH2:25][O:26][CH3:27])([C:20]([F:23])([F:22])[F:21])[C:16]([F:19])([F:18])[F:17])=[CH:11][C:10]=2[CH2:28][CH2:29][CH3:30])=[CH:4][C:3]=1[CH2:31]O.[CH3:33][C:34]1([C:41]2[CH:46]=[CH:45][C:44]([O:47][CH:48]([CH3:50])[CH3:49])=[CH:43][CH:42]=2)[NH:38][C:37](=[O:39])[NH:36][C:35]1=[O:40].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.O1CCCC1>O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]([O:24][CH2:25][O:26][CH3:27])([C:16]([F:17])([F:18])[F:19])[C:20]([F:23])([F:22])[F:21])=[CH:11][C:10]=2[CH2:28][CH2:29][CH3:30])=[CH:4][C:3]=1[CH2:31][N:36]1[C:35](=[O:40])[C:34]([C:41]2[CH:46]=[CH:45][C:44]([O:47][CH:48]([CH3:50])[CH3:49])=[CH:43][CH:42]=2)([CH3:33])[NH:38][C:37]1=[O:39]
Reactant: CCCc1cc(C(OCOC)(C(F)(F)F)C(F)(F)F)ccc1Oc1ccc(Cl)c(CO)c1
Reactant: CC(C)Oc1ccc(C2(C)NC(=O)NC2=O)cc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: O
Product: CCCc1cc(C(OCOC)(C(F)(F)F)C(F)(F)F)ccc1Oc1ccc(Cl)c(CN2C(=O)NC(C)(c3ccc(OC(C)C)cc3)C2=O)c1
Yield: 50 %

Procedure:
(2-Chloro-5-(4-(1,1,1,3,3,3-hexafluoro-2-(methoxymethoxy)propan-2-yl)-2-propylphenoxy) phenyl)methanol (10 mg, 0.0212 mmol), 5-methyl-5-(4-(1-methylethoxy)phenyl)imidazolidine-2,4-dione (16 mg, 0.0635 mmol) and triphenylphosphine (16 mg, 0.0635 mmol) were added and dried in vacuo. N, N-dimethylformamide (300 μL) was added, and under ice-cold conditions, a solution of diethyl azodicarboxylate in tetrahydrofuran (29 μL, 0.0635 mmol) was added. The resultant mixture was stirred at room temperature for 4 hours. The reaction solution was added with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, concentrated in vacuo, and purified using preparative thin-layer chromatography (hexane/ethyl acetate). 3-(2-Chloro-5-(4-(1,1,1,3,3,3-hexafluoro-2-(methoxymethoxy)propan-2-yl)-2-propylphenoxy) benzyl)-5-(4-(1-methylethoxy)phenyl)-5-methylimidazolidine-2,4-dione (7.6 mg, yield >100%) was obtained as a yellow oil.
Reaction SMILES: [H-].[Na+].[N+:3]([C:6]1[CH:14]=[C:13]([CH2:15][CH3:16])[CH:12]=[C:11]([N+:17]([O-:19])=[O:18])[C:7]=1[NH:8][O:9][CH3:10])([O-:5])=[O:4].[CH2:20](Br)[CH:21]=[CH2:22]>CN(C)C=O>[CH2:22]([N:8]([O:9][CH3:10])[C:7]1[C:6]([N+:3]([O-:5])=[O:4])=[CH:14][C:13]([CH2:15][CH3:16])=[CH:12][C:11]=1[N+:17]([O-:19])=[O:18])[CH:21]=[CH2:20]
Reactant: C=CCBr
Reactant: CCc1cc([N+](=O)[O-])c(NOC)c([N+](=O)[O-])c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C=CCN(OC)c1c([N+](=O)[O-])cc(CC)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 70 %

Procedure:
To 0.017 mole of sodium hydride, obtained from 0.82 g. of a 50% dispersion of sodium hydride in mineral oil (by the process described in Example 6, supra), was added 50 ml. of dimethylformamide. To the suspension was added 3.0 g. (0.012 mole) of 2,6-dinitro-4-ethyl-N-methoxyaniline (Preparation 2), and the mixture stirred for about 5-10 minutes. Allyl bromide, 2.9 g. (0.024 mole), was added and the reaction mixture stirred at room temperature for about 30 minutes. A sample of the reaction mixture checked by NMR showed the presence of about 70-80 percent of the desired product, together with about 20-30 percent of starting material. The reaction mixture was then heated at about 90° C., with stirring, for about an hour. A check by NMR indicated the reaction had gone to completion. The reaction product mixture was worked up by adding dilute aqueous hydrochloric acid and toluene. The organic layer was separated and dried over anhydrous magnesium sulfate. The drying agent was filtered off and the filtrate was chromatographed on a Florisil column. The fractions were examined by NMR spectrum, combined, and concentrated in vacuo to dryness. The residue was recrystallized from petroleum ether (b.p. 60°-71° C.) to give 1.7 g. of product having a melting point of about 83°-85° C. The product was identified by NMR spectrum and elemental analyses as N-allyl-2,6-dinitro-4-ethyl-N-methoxyaniline.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[N:11]([C:12]3[CH:17]=[CH:16][C:15]([S:18](=[O:21])(=[O:20])[NH2:19])=[CH:14][CH:13]=3)[CH2:10][CH2:9][C:8]([C:22]([O:24][CH3:25])=[O:23])=[CH:7][C:6]=2[CH:26]=1.B([O-])([O-])O[C:29]1[CH:34]=[CH:33][C:32]([O:35][CH2:36][CH2:37][O:38][CH2:39][CH2:40][CH2:41][CH3:42])=[CH:31][CH:30]=1.C(=O)([O-])[O-].[K+].[K+].C(O)C>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.C1(C)C=CC=CC=1>[CH2:39]([O:38][CH2:37][CH2:36][O:35][C:32]1[CH:31]=[CH:30][C:29]([C:2]2[CH:3]=[CH:4][C:5]3[N:11]([C:12]4[CH:13]=[CH:14][C:15]([S:18](=[O:20])(=[O:21])[NH2:19])=[CH:16][CH:17]=4)[CH2:10][CH2:9][C:8]([C:22]([O:24][CH3:25])=[O:23])=[CH:7][C:6]=3[CH:26]=2)=[CH:34][CH:33]=1)[CH2:40][CH2:41][CH3:42]
Reactant: COC(=O)C1=Cc2cc(Br)ccc2N(c2ccc(S(N)(=O)=O)cc2)CC1
Reactant: CCCCOCCOc1ccc(OB([O-])[O-])cc1
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: [K+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)OC)CCN3c2ccc(S(N)(=O)=O)cc2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 87.1 %

Procedure:
A mixture of methyl 7-bromo-1-(4-sulfamoylphenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate (0.31 g), 4-(2-butoxyethoxy)phenyl borate (0.22 g), 1M potassium carbonate solution (3 ml), ethanol (5 ml) and toluene (50 ml) was stirred under argon atmosphere at room temperature for 30 minutes. To the mixture was added tetrakis(triphenylphosphine)palladium (0.04 g), and the mixture was refluxed under argon atmosphere for 3 hours and extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried with anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified with silica gel column chromatography (ethyl acetate/hexane) to give methyl 7-[4-(2-butoxyethoxy)phenyl]-1-(4-sulfamoylphenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate (0.34 g) as yellow crystals.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[I:12])[C:5](OC)=[O:6].[BH4-].[Li+]>O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]([CH2:5][OH:6])[CH:9]=[CH:10][C:11]=1[I:12]
Reactant: COC(=O)c1ccc(I)c(Br)c1
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Product: OCc1ccc(I)c(Br)c1
Reaction time: 36 h
Yield: 65.5 %

Procedure:
To a solution of methyl 3-bromo-4-iodobenzoate (110.0 mg, 0.322 mmol) in tetrahydrofuran (2 mL) was added 2 M lithium tetrahydroborate in tetrahydrofuran (0.161 mL) at room temperature. After stirring for 36 h, the reaction was quenched with sat. ammonium chloride solution, diluted with diethyl ether. The aqueous phase was extract with diethyl ether once. The combined organic solutions were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified with silica gel chromatography (5% to 20% ethyl acetate/hexane) to give a white solid (66 mg, 65%). 1H NMR (400 MHz, CDCl3): δ 7.82 (d, J=8.2 Hz, 1H), 7.63 (m, 1H), 6.98 (m, 1H), 4.63 (s, 2H). LCMS found for C7H5BrI (M+H−H2O)+: m/z=295, 297.
Reaction SMILES: [OH:1][CH2:2][CH2:3][O:4][C:5]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH2:14][CH2:15][OH:16])[C:6]=1[CH:7]=O.C([O-])(=O)C.[NH4+].C([BH3-])#[N:23].[Na+].[ClH:26]>CO>[ClH:26].[OH:1][CH2:2][CH2:3][O:4][C:5]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH2:14][CH2:15][OH:16])[C:6]=1[CH2:7][NH2:23]
Reactant: [BH3-]C#N
Reactant: O=Cc1c(OCCO)cccc1OCCO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [NH4+]
Solvent: CO
Product: NCc1c(OCCO)cccc1OCCO
Reaction time: 48 h
Yield: 92 %

Procedure:
5.08 g of 2,6-bis(2-hydroxyethoxy)benzaldehyde dissolved in 100 ml of anhydrous methanol are treated with 15.6 g of ammonium acetate and 12 g of sodium cyanoborohydride, then stirred under nitrogen blanket at 25°-30° C. for 48 hours, then adjusted to pH=1 with concentrated hydrochloric acid and evaporated at reduced pressure. The solid residue is treated with 30 ml of water and extracted with 20 ml of ethyl acetate, said volume being divided previously into two portions. The water phase, after elimination of the small amount of ethyl acetate dissolved, such removal being carried out under reduced pressure, is adjusted to pH=11 with a 25% solution of potassium hydroxide and then extracted with tetrahydrofuran. The extracts are dried with anhydrous potassium carbonate, then evaporated under reduced pressure, dissolved with 30 ml of a 1/1 mixture of tetrahydrofuran/ethyl ether, and afterwards saturated with gaseous hydrogen chloride and filtered. The solid, after washing with anhydrous ethyl ether, drying under reduced pressure and crystallization from a mixture of ethanol/acetonitrile, gives 2,6-bis(hydroxyethoxy)benzylamine hydrochloride with a yield of 92%; melting point is 166°-168° C. I.R. (KBr), 3325 cm-1 (OH), 2605 cm-1 (NH3+), 1262 cm-1 (aromatic C--O), 779 cm-1 (phenyl).
Reaction SMILES: C1OCC2C1=CC=CC=2.ON1[C:15](=[O:16])[C:14]2=[CH:17][CH:18]=[CH:19][CH:20]=[C:13]2[C:12]1=[O:21]>C(#N)C>[CH:12](=[O:21])[C:13]1[C:14](=[CH:17][CH:18]=[CH:19][CH:20]=1)[CH:15]=[O:16]
Reactant: O=C1c2ccccc2C(=O)N1O
Agent: c1ccc2c(c1)COC2
Solvent: CC#N
Product: O=Cc1ccccc1C=O
Temperature: 60 °C
Reaction time: 8 h
Yield: 1 %

Procedure:
To a mixture of 10 mmol of phthalan (isocoumaran), 1 mmol of N-hydroxyphthalimide, and 5 ml of acetonitrile was introduced 10 mmol of nitrogenmonoxide, and the resultantmixture was stirred at 60° C. for 8 hours. Isolation of products in the reaction mixture by column chromatography on a silica gel revealed that phthalan was converted, at a rate of 15%, into phthalaldehyde (yield: 1%), 1-hydroxyphthalan (yield: 3%), NHPI adduct (yield: 3%), and an acetamide compound (yield: 3%).
Reaction SMILES: CC(C)([O-])C.[K+].[Br-].[F:8][CH2:9][CH2:10][CH2:11][CH2:12][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O=[C:33]1[CH2:38][CH2:37][CH:36]([NH:39][C:40](=[O:46])[O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[CH2:35][CH2:34]1.[Cl-].[NH4+]>O1CCCC1>[F:8][CH2:9][CH2:10][CH2:11][CH:12]=[C:33]1[CH2:38][CH2:37][CH:36]([NH:39][C:40](=[O:46])[O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[CH2:35][CH2:34]1
Reactant: CC(C)(C)OC(=O)NC1CCC(=O)CC1
Reactant: FCCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: [Br-]
Agent: [Cl-]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NC1CCC(=CCCCF)CC1
Reaction time: 0.5 h
Yield: 62.9 %

Procedure:
To a mixture of potassium t-butoxide (0.54 g) and tetrahydrofuran (10 ml) at room temperature was added 4-fluorobutyltriphenylphosphonium bromide (2.0 g). After stirring for 30 minutes, a solution of t-butyl 4-oxocyclohexylcarbamate (0.50 g) in tetrahydrofuran (5 ml), and the mixture was stirred at room temperature. After 10 hours, saturated aqueous ammonium chloride was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and then dried over sodium sulfate, and the solvent was evaporated under reduced pressure from the organic layer. The residue was suspended in hexane and the suspension was stirred at 40° C. After 20 minutes, the precipitate was filtrated off, and the filtrate was concentrated under reduced pressure to give 400 mg of t-butyl [4-(4-fluorobutylidene)cyclohexyl]-carbamate.