Hydrochloric Acid → HCID 70049329, compound

HRID 1780249Notes

Reaction equation

HRID 1780249 reaction equation
[Br:1][CH2:2][C:3](Cl)=[O:4].C(N(CC)CC)C.Cl.[CH3:14][NH:15][C:16]1[CH:58]=[CH:57][C:19]([O:20][CH2:21][C:22]([NH:24][C@H:25]([C:30]([NH:32][C@@H:33]([CH2:50][C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[C@H:34]([OH:49])[C:35]([N:37]2[CH2:48][CH2:47][CH2:46][C@H:38]2[C:39]([NH:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])=[O:36])=[O:31])[CH2:26][C:27](=[O:29])[NH2:28])=[O:23])=[CH:18][CH:17]=1.Cl>CN(C)C=O>[Br:1][CH2:2][C:3]([N:15]([C:16]1[CH:17]=[CH:18][C:19]([O:20][CH2:21][C:22]([NH:24][C@H:25]([C:30]([NH:32][C@@H:33]([CH2:50][C:51]2[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=2)[C@H:34]([OH:49])[C:35]([N:37]2[CH2:48][CH2:47][CH2:46][C@H:38]2[C:39]([NH:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])=[O:36])=[O:31])[CH2:26][C:27](=[O:29])[NH2:28])=[O:23])=[CH:57][CH:58]=1)[CH3:14])=[O:4]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 89602Bromoacetyl chlorideHCID 70050717HCID 70050717, compound

Product 1

HCID 70049329HCID 70049329, compoundYield 68.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.59 ml (7.2 mmol) of bromoacetyl chloride and 1.6 ml (11.7 mmol) of triethylamine were added, whilst ice-cooling, to a solution of 3.0 g (4.5 mmol) of 1-[(2S,3S)-3-{N2 -[4-(methylamino)phenoxyacetyl]-L-asparaginyl}amino-2-hydroxy-4-phenylbutyryl]-N-t-butyl-L-prolinamide hydrochloride (prepared as described in Example 20) in 10 ml of dimethylformamide, and the resulting mixture was stirred for 1 day. At the end of this time, the reaction mixture was neutralized by the addition of 1N aqueous hydrochloric acid. It was then concentrated by evaporation under reduced pressure, and the concentrate was diluted with ethyl acetate. The resulting diluted solution was washed with 1N aqueous hydrochloric acid, with a 5% w/v aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order. It was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure, and the residue was purified by column chromatography, using a 1:15 by volume mixture of methanol and methylene chloride as the eluent, to give 2.3 g of the title compound as a colorless powder, melting at 116°-122° C.

Workup

  1. concentrationIt was then concentrated by evaporation under reduced pressure
  2. additionthe concentrate was diluted with ethyl acetate
  3. washThe resulting diluted solution was washed with 1N aqueous hydrochloric acid, with a 5% w/v aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order
  4. dry with materialIt was then dried over anhydrous sodium sulfate
  5. customThe solvent was removed by distillation under reduced pressure
  6. customthe residue was purified by column chromatography
  7. additionby volume mixture of methanol and methylene chloride as the eluent

Sources & evidence

ORD record
ord-8538f5c8b2f94d228db1ea1e8ada4180
Source dataset
uspto-grants-1997_05
Patent number
US05629406

Reaction notes

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