Hydrochloric Acid → HCID 10771214, compound

HRID 1859643Notes

Reaction equation

HRID 1859643 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:17](=[O:18])[N:16]([CH2:19][C:20]([NH:22][CH:23]([CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH:24]([OH:38])[C:25]([C:28](=[O:37])[NH:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)([F:27])[F:26])=[O:21])[C:15]([C:46]2[CH:51]=[CH:50][CH:49]=[C:48]([Cl:52])[CH:47]=2)=[N:14][CH:13]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(C)C=CC=CC=1.ClC(Cl)C(O)=O.Cl>CS(C)=O>[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:17](=[O:18])[N:16]([CH2:19][C:20]([NH:22][CH:23]([CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:24](=[O:38])[C:25]([C:28](=[O:37])[NH:29][CH2:30][C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)([F:26])[F:27])=[O:21])[C:15]([C:46]2[CH:51]=[CH:50][CH:49]=[C:48]([Cl:52])[CH:47]=2)=[N:14][CH:13]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 6597Dichloroacetic AcidHCID 10556891HCID 10556891, compound

Product 1

HCID 10771214HCID 10771214, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of the objective compound of step (14) (69 g, 95 mmol) and WSCIHCl (99.87 g, 0.5209 mol) in DMSO (590 mL)-toluene (590 mL) was added dichloroacetic acid (15.6 mL) with drop wise over 20 minutes under ice-cooling. The resulting mixture was stirred under ice-cooling for 2.5 hours, then added to 0.5 M hydrochloric acid (1800 mL) and extracted with ethyl acetate (1800 mL, 2×800 mL). The extract was washed with saturated sodium hydrogencarbonate aqueous solution (800 mL) and saturated brine (800 mL), dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (99:1 chloroform-methanol) to give 52.95 g (77%) of 2-[5-benzyloxycarbonylamino-2-(3-chlorophenyl)-1,6-dihydro-6-oxo-1-pyrimidinyl]-N-[1-benzyl-3-[N-(benzyl)carbamoyl]-3,3-difluoro-2-oxopropyl]acetamide as a white solid.

Workup

  1. temperaturecooling
  2. temperaturecooling for 2.5 hours
  3. extractionextracted with ethyl acetate (1800 mL, 2×800 mL)
  4. washThe extract was washed with saturated sodium hydrogencarbonate aqueous solution (800 mL) and saturated brine (800 mL)
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (99:1 chloroform-methanol)

Sources & evidence

ORD record
ord-780cb2a885f5401bb2cff8e4642ff7a1
Source dataset
uspto-grants-2003_03
Patent number
US06528514B1

Reaction notes

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