Benzyloxyamine hydrochloride → HCID 19101709, compound

HRID 1974642Notes

Reaction equation

HRID 1974642 reaction equation
[CH2:1]([NH:8][C:9]1[C:17]2[N:16]=[C:15]([CH2:18][C:19]([NH2:21])=[O:20])[N:14](C3CC3)[C:13]=2[C:12]([F:25])=[C:11]([N:26]2[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]2)[C:10]=1[F:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH2:35]([O:42]N)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.[C:44](=O)(O)[O-].[Na+].O.[CH2:50](O)[CH3:51]>>[CH2:1]([NH:8][C:9]1[C:17]2[N:16]([CH:51]3[CH2:50][CH2:44]3)[C:15]([CH2:18][C:19]([NH:21][O:42][CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[O:20])=[N:14][C:13]=2[C:12]([F:25])=[C:11]([N:26]2[CH2:27][CH2:28][N:29]([CH3:32])[CH2:30][CH2:31]2)[C:10]=1[F:33])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 4

HCID 102312Benzyloxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 19096565Water ethanolHCID 19101708HCID 19101708, compound

Product 1

HCID 19101709HCID 19101709, compoundYield 48%

Conditions

Temperature
60 °C

Procedure

4-(Benzylamino)-1-cyclopropyl-5,7-difluoro-6-(4-methyl-1-piperazinyl)-2-benzimidazoleacetamide (4.4 g, 9.7 mmol) and O-benzyl-hydroxylamine hydrochloride (6.2 g, 38.8 mmol) are suspended in water-ethanol (1:1; 100 ml) and warmed to 60° C. for two days. After cooling, the pH is adjusted to 5-6 with saturated aqueous sodium bicarbonate solution and the resulting solution extracted with ethyl acetate. The combined organic layers are dried (magnesium sulfate), concentrated and chromatographed on silica gel (eluent: 5% then 15% methanol-dichloromethane), affording 2.6 g of 2-[7-benzylamino-1-cyclopropyl-4.6-difluoro-5-(4-methyl-piperazin-1-yl)-1H-benzimidazol-2-yl]-N-benzyloxy-acetamide (48%): NMR (CDCl3): 1.04 (m,4H),2.42(s,3H),2.65 (m,4H), 3.27 (m,5H), 3.93(s,2H),4.67(s,2H),4.89(s,2H),7.20-7.39(m,10H), 10.47(s,1H).

Workup

  1. temperatureAfter cooling
  2. extractionthe resulting solution extracted with ethyl acetate
  3. dry with materialThe combined organic layers are dried (magnesium sulfate)
  4. concentrationconcentrated
  5. customchromatographed on silica gel (eluent

Sources & evidence

ORD record
ord-48fc65d54cfa4ada9e547e65baec6d50
Source dataset
uspto-grants-1994_02
Patent number
US05283248

Reaction notes

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