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

HRID 1350636Notes

Reaction equation

HRID 1350636 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-37b1174dc9f04dc3b02954e2b345af00
Source dataset
uspto-grants-2007_05
Patent number
US07214800B2

Reaction notes

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