Dimethylformamide → 2-[(R)-1-(3-Toluoyloxy-2-oxo-propylamino)-2-methyl-propyl]-3-benzyl-7-chloro-3H-quinazolin-4-one

HRID 490269Notes

Reaction equation

HRID 490269 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].CCN([CH:31]([CH3:33])[CH3:32])C(C)C.[C:34]1(C)[C:35]([C:40]([O:42]CC(=O)CBr)=[O:41])=[CH:36]C=C[CH:39]=1.[C:49](Cl)(=[O:56])[C:50]1C=CC=CC=1.[CH3:58]N(C=O)C>>[C:31]1([CH3:32])[CH:33]=[CH:39][CH:34]=[C:35]([C:40]([O:42][N:1]([CH2:58][C:49](=[O:56])[CH3:50])[C@@H:2]([C:6]2[N:15]([CH2:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:14](=[O:23])[C:13]3[C:8](=[CH:9][C:10]([Cl:24])=[CH:11][CH:12]=3)[N:7]=2)[CH:3]([CH3:5])[CH3:4])=[O:41])[CH:36]=1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 7412Benzoyl chlorideHCID 81531DiisopropylethylamineHCID 21015281(R)-2-(1-amino-2-methylpropyl)-3-benzyl-7-chloroquinazolin-4(3H)-oneHCID 865918921-Toluoyloxy-3-bromopropan-2-one

Product 1

HCID 210969932-[(R)-1-(3-Toluoyloxy-2-oxo-propylamino)-2-methyl-propyl]-3-benzyl-7-chloro-3H-quinazolin-4-one

Procedure

To 2-((R)-1-amino-2-methyl-propyl)-3-benzyl-7-chloro-3H-quinazolin-4-one (1.0 g, 2.9 mMol) in DMF (10 mL) was added DIEA (0.6 mL, 3.4 mMol) and 1-toluoyloxy-3-bromopropan-2-one (1.0 g, 3.7 mMol) (Prepared using the procedure of F. C. Hartman, Biochemistry, 9, 1776 (1970) except substituting toluoyl chloride for benzoyl chloride.) The reaction was stirred at RT for 18 h, concentrated under vacuum, taken up in EtOAc, washed with 1 N Na2CO3, dried (Na2SO4) and evaporated to dryness. The product was converted to its hydrochloride salt by treating with 4 N HCl in dioxane (20 mL) and concentration under vacuum. Trituration with (1:1) Et2O/pet. ether, filtration and drying under vacuum left the title compound (1.87 g, 100%, 88% pure) as a beige solid: MS (ES) m/e 532.2 (M+H)+.

Workup

  1. customPrepared
  2. concentrationconcentrated under vacuum
  3. washwashed with 1 N Na2CO3
  4. dry with materialdried (Na2SO4)
  5. customevaporated to dryness
  6. additionby treating with 4 N HCl in dioxane (20 mL) and concentration under vacuum
  7. filtrationTrituration with (1:1) Et2O/pet. ether, filtration
  8. customdrying under vacuum
  9. waitleft the title compound (1.87 g, 100%, 88% pure) as a beige solid

Sources & evidence

ORD record
ord-96864ef6ebe74d3d86a116a31d51dea7
Source dataset
uspto-grants-2009_05
Patent number
US07528137B2

Reaction notes

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