Sodium triacetoxyborohydride → ((S)-1-{[(R)-1-(3-Benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-2-methyl-propylamino]-methyl}-4-benzyloxycarbonylamino-butyl)-carbamic acid tert-butyl ester

HRID 490270Notes

Reaction equation

HRID 490270 reaction equation
[NH2:1][C@@H:2]([C:6]1[N:15]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:14](=[O:23])[C:13]2[C:8](=[CH:9][C:10]([Cl:24])=[CH:11][CH:12]=2)[N:7]=1)[CH:3]([CH3:5])[CH3:4].[C:25]([O:29][C:30](=[O:49])[NH:31][C@H:32]([CH:47]=O)[CH2:33][CH2:34][CH2:35][NH:36][C:37]([O:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:38])([CH3:28])([CH3:27])[CH3:26].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[C:25]([O:29][C:30](=[O:49])[NH:31][C@H:32]([CH2:47][NH:1][C@@H:2]([C:6]1[N:15]([CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:14](=[O:23])[C:13]2[C:8](=[CH:9][C:10]([Cl:24])=[CH:11][CH:12]=2)[N:7]=1)[CH:3]([CH3:5])[CH3:4])[CH2:33][CH2:34][CH2:35][NH:36][C:37]([O:39][CH2:40][C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)=[O:38])([CH3:28])([CH3:26])[CH3:27]

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 21015281(R)-2-(1-amino-2-methylpropyl)-3-benzyl-7-chloroquinazolin-4(3H)-oneHCID 86591893((S)-4-benzyloxycarbonylamino-1-formyl-butyl)-carbamic acid tert-butyl ester

Product 1

HCID 69078749((S)-1-{[(R)-1-(3-Benzyl-7-chloro-4-oxo-3,4-dihydro-quinazolin-2-yl)-2-methyl-propylamino]-methyl}-4-benzyloxycarbonylamino-butyl)-carbamic acid tert-butyl esterYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-((R)-1-amino-2-methyl-propyl)-3-benzyl-7-chloro-3H-quinazolin-4-one (a compound of Formula 107, 366 mg, 1.07 mmol) and ((S)-4-benzyloxycarbonylamino-1-formyl-butyl)-carbamic acid tert-butyl ester (prepared as previously described: Hamada, Y.; Shioro, T. Chem. Pharm. Bull. 1982, 30, 1921) (452 mg, 1.29 mmol) in CH2Cl2 (25 mL) was added sodium triacetoxyborohydride (341 mg, 1.61 mmol). The resultant cloudy mixture was stirred overnight and quenched with saturated brine (50 mL). The aqueous layer was extracted with CH2Cl2 (20 mL) and the combined extracts were dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (2:1 hexanes:ethyl acetate) to provide 550 mg (76%) of the title compound as a yellow oil. MS(ES+) m/e 676.4 [M+H]+.

Workup

  1. customquenched with saturated brine (50 mL)
  2. extractionThe aqueous layer was extracted with CH2Cl2 (20 mL)
  3. dry with materialthe combined extracts were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography (2:1 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-7c06b2dbd76c48debb67d7cca7e42a9f
Source dataset
uspto-grants-2009_05
Patent number
US07528137B2

Reaction notes

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