HCID 69075315, compound → (3-{(S)-1-[(R)-1-(3-Benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-2-methyl-propyl]-2-p-tolyl-4,5-dihydro-1H-imidazol-4-yl}-propyl)-carbamic acid benzyl ester

HRID 490272Notes

Reaction equation

HRID 490272 reaction equation
C(OC(=O)[NH:7][CH:8]([CH2:23][N:24]([CH:34]([C:38]1[N:47]([CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C:46](=[O:55])[C:45]2[C:40](=[CH:41][C:42]([Cl:56])=[CH:43][CH:44]=2)[N:39]=1)[CH:35]([CH3:37])[CH3:36])[C:25]([C:27]1[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=1)=O)[CH2:9][CH2:10][CH2:11][NH:12][C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])(C)(C)C>C(Cl)Cl.C(O)(C(F)(F)F)=O>[CH2:16]([O:15][C:13](=[O:14])[NH:12][CH2:11][CH2:10][CH2:9][C@H:8]1[CH2:23][N:24]([C@@H:34]([C:38]2[N:47]([CH2:48][C:49]3[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=3)[C:46](=[O:55])[C:45]3[C:40](=[CH:41][C:42]([Cl:56])=[CH:43][CH:44]=3)[N:39]=2)[CH:35]([CH3:37])[CH3:36])[C:25]([C:27]2[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=2)=[N:7]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

3

Reactant 1

HCID 69075315HCID 69075315, compound

Product 1

HCID 58861274(3-{(S)-1-[(R)-1-(3-Benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-2-methyl-propyl]-2-p-tolyl-4,5-dihydro-1H-imidazol-4-yl}-propyl)-carbamic acid benzyl esterYield 40%

Reagents, catalysts & solvents 1

HCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

A solution of (1-([[1-(3-benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-2-methyl-propyl]-(1-p-tolyl-methanoyl)-amino]-methyl}-4-benzyloxycarbonylamino-butyl)-carbamic acid tert-butyl ester (235 mg, 0.37 mmol) in CH2Cl2/TFA (4:1, 5 mL) was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and the residue was diluted with CH2Cl2 (10 mL) and washed with saturated aqueous NaHCO3 (10 mL). The aqueous layer was extracted with CH2Cl2 and the combined extracts were dried over MgSO4, filtered and concentrated under reduced pressure. The residue was diluted with THF (10 mL) and saturated aqueous NaHCO3 (1 mL). The mixture was stirred at room temperature for 10 days, diluted with ether (20 mL) and washed with brine. The aqueous layer was extracted with two 10 mL portions of EtOAc and the combined extracts were dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (19:1 CH2Cl2:MeOH) to provide 81 mg (40%) of the title compound as a pale white powder. MS(ES+) m/e 675.6 [M+H]+.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionthe residue was diluted with CH2Cl2 (10 mL)
  3. washwashed with saturated aqueous NaHCO3 (10 mL)
  4. extractionThe aqueous layer was extracted with CH2Cl2
  5. dry with materialthe combined extracts were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. additionThe residue was diluted with THF (10 mL) and saturated aqueous NaHCO3 (1 mL)
  9. additiondiluted with ether (20 mL)
  10. washwashed with brine
  11. extractionThe aqueous layer was extracted with two 10 mL portions of EtOAc
  12. dry with materialthe combined extracts were dried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customThe residue was purified by silica gel chromatography (19:1 CH2Cl2:MeOH)

Sources & evidence

ORD record
ord-721901a0111e46a496663db86eec632c
Source dataset
uspto-grants-2009_05
Patent number
US07528137B2

Reaction notes

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