Dimethylformamide → HCID 18438089, compound

HRID 1643223Notes

Reaction equation

HRID 1643223 reaction equation
[CH2:1]([N:5]1[C:9]([CH2:10][N:11]([CH2:17][C:18]2[CH:19]=[C:20]3[C:24](=[CH:25][CH:26]=2)[NH:23][CH:22]=[CH:21]3)[CH2:12][CH2:13][CH:14]([CH3:16])[CH3:15])=[C:8]([Cl:27])[N:7]=[C:6]1[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[CH3:34])[CH2:2][CH2:3][CH3:4].ClS([N:39]=[C:40]=O)(=O)=O.CN(C=O)C.[OH-].[NH4+]>C(#N)C>[CH2:1]([N:5]1[C:9]([CH2:10][N:11]([CH2:17][C:18]2[CH:19]=[C:20]3[C:24](=[CH:25][CH:26]=2)[NH:23][CH:22]=[C:21]3[C:40]#[N:39])[CH2:12][CH2:13][CH:14]([CH3:15])[CH3:16])=[C:8]([Cl:27])[N:7]=[C:6]1[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[CH3:34])[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 14923Ammonium HydroxideHCID 70918Chlorosulfonyl isocyanateHCID 18437858HCID 18437858, compound

Product 1

HCID 18438089HCID 18438089, compoundYield 6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent3×

Procedure

To an ice-cooled solution of 5-{[(3-butyl-5-chloro-2-o-tolyl-3H-imidazol-4-ylmethyl)-(3-methyl-butyl)-amino]-methyl}-1H-indole (173 mg, 0.363 mmol) in 5 ml of anhydrous acetonitrile under nitrogen is added a solution of chlorosulfonyl isocyanate (69.5 mg, 0.491 mmol, 1.35 eq.) in 1 ml of acetonitrile, after stirring for 20 mim, a solution of DMF (30.1 mg) in 2 ml of acetonitrile is added dropwise, stirred for additional 1 h. The reaction mixture is poured into ice water and basified with diluted ammonium hydroxide solution; the mixture is extracted with dichloromethane, dried over sodium sulfate. The solvent is evaporated; the residue is purified through flash chromatography to give 11 mg of 5-{[(3-butyl-5-chloro-2-o-tolyl-3H-imidazol-4-ylmethyl)-(3-methyl-butyl)-amino]-methyl}-1H-indole-3-carbonitrile as white solid. 1H NMR (400 MHz, CDCl3) δ 7.63 (1H, s), 7.38 (1H, d, J=3Hz), 7.15˜7-36 (4H, m), 7.07 (4H, dd, J=1.2, 8.4 Hz), 6.89-6.93 (2H, m), 3.73 (2H, t, J=7.5 Hz), 3.65 (2H, s), 3.57 (2H, s), 2.55 (2H, d, f=6.9 Hz), 2.02 (3H, s), 1.62 (1H, m), 1.46 (2H, q, J=6.6 Hz), 1.14 (2H, m), 0.85 (6H, d, J=6.6 Hz), 0.75 (2H, m), 0.51 (3H, t, J=7.2 Hz); MS (+VE) m/z 502 (M+1).

Workup

  1. stirringstirred for additional 1 h
  2. extractionthe mixture is extracted with dichloromethane
  3. dry with materialdried over sodium sulfate
  4. customThe solvent is evaporated
  5. customthe residue is purified through flash chromatography

Sources & evidence

ORD record
ord-c8ac729d1ee144f8bd502afe13da1194
Source dataset
uspto-grants-2012_02
Patent number
US08119665B2

Reaction notes

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