Water → N'-(2,4-difluorophenyl)-N-heptyl-N-[5-(4,5,6,7-tetrahydro-1H-benzimidazol-2-ylthio)pentyl]urea

HRID 486088

Reaction equation

HRID 486088 reaction equation
[H-].[Na+].[N:3]1[C:4](=[S:12])[N:5]=[C:6]2[CH2:11][CH2:10][CH2:9][CH2:8][C:7]=12.Br[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][N:19]([CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[C:20]([NH:22][C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=1[F:30])=[O:21].O>CN(C)C=O>[F:30][C:24]1[CH:25]=[C:26]([F:29])[CH:27]=[CH:28][C:23]=1[NH:22][C:20](=[O:21])[N:19]([CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][S:12][C:4]1[NH:5][C:6]2[CH2:11][CH2:10][CH2:9][CH2:8][C:7]=2[N:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 10342005N-(5-bromopentyl)-N'-(2,4-difluorophenyl)-N-heptylureaHCID 190975414,5,6,7-Tetrahydrobenzimidazol-2-thione

Product 1

HCID 19097543N'-(2,4-difluorophenyl)-N-heptyl-N-[5-(4,5,6,7-tetrahydro-1H-benzimidazol-2-ylthio)pentyl]ureaYield 18.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Part B. To a suspension of sodium hydride (0.099 g, 0.004 mol; washed free of the mineral oil with hexane) in N,N-dimethylformamide (15 ml) under a nitrogen atmosphere, cooled to 0°, 4,5,6,7-tetrahydrobenzimidazol-2-thione (0.50 g, 0.0033 mol) was added slowly. The reaction mixture was stirred for two hours and then a solution of N-(5-bromopentyl)-N'-(2,4-difluorophenyl)-N-heptyl urea (1.38 g, 0.0033 mol) in N,N-dimethylformamide (5 ml) was added. The reaction mixture was stirred at 0° for one hour, at ambient temperature for one hour, then was poured into water (50 ml) and extracted with ethyl acetate (2×50 ml). The combined organic extracts were washed with water and brine, then dried over magnesium sulfate and concentrated to give the crude product. The product was purified by flash chromatography on silica gel (250 ml) eluting with hexane: ethyl acetate (50:50::v:v) to give the title compound as a solid (0.30 g, 0.0006 mol), mp 98°-100°. 1H NMR (CDCl3) δ10.0-9.4 (bs,1H), 8.05-7.87 (m,1H), 6.91-6.75 (m,2H), 6.5-6.41 (d,1H,J=3.75 Hz), 3.42-3.2 (m,4H), 2.96-2.85 (t,2H,J=6.0 Hz), 2.61-2.45 (m,4H), 1.81-1.22 (m,20H), 0.88 (t,3H,J=6.5 Hz).

Workup

  1. washwashed free of the mineral oil with hexane) in N,N-dimethylformamide (15 ml) under a nitrogen atmosphere
  2. temperaturecooled to 0°
  3. stirringThe reaction mixture was stirred at 0° for one hour, at ambient temperature for one hour
  4. extractionextracted with ethyl acetate (2×50 ml)
  5. washThe combined organic extracts were washed with water and brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customto give the crude product
  9. customThe product was purified by flash chromatography on silica gel (250 ml)
  10. washeluting with hexane: ethyl acetate (50:50::v:v)

Sources & evidence

ORD record
ord-4144f0a05c8c41aea1df34a5f222875e
Source dataset
uspto-grants-1994_03
Patent number
US05290801

Linked notes

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