Triphenylphosphine → (2R)-N,N-dimethyl-2-[(4-oxo-3,4-dihydroquinazolin-5-yl)oxy]propanamide

HRID 1162207Notes

Reaction equation

HRID 1162207 reaction equation
C(OC[N:9]1[C:18](=[O:19])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][C:16]=2[OH:20])[N:11]=[CH:10]1)(=O)C(C)(C)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:40][N:41]([CH3:47])[C:42](=[O:46])[C@H:43]([CH3:45])O>C(Cl)Cl>[CH3:40][N:41]([CH3:47])[C:42](=[O:46])[C@H:43]([O:20][C:16]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:17]=1[C:18](=[O:19])[NH:9][CH:10]=[N:11]2)[CH3:45]

Participants

5

Reactant 3

HCID 11776TriphenylphosphineHCID 816822(2s)-2-Hydroxy-n,n-dimethylpropanamideHCID 68496163(5-hydroxy-4-oxoquinazolin-3(4H)-yl)methyl pivalate

Product 1

HCID 136346624(2R)-N,N-dimethyl-2-[(4-oxo-3,4-dihydroquinazolin-5-yl)oxy]propanamideYield 71.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

DTAD (13.34 g, 58 mmol) was added portion-wise to an ice-cooled solution of (5-hydroxy-4-oxoquinazolin-3(4H)-yl)methyl pivalate (8 g, 29 mmol), triphenylphosphine (15.2 g, 58 mmol) and (S)—N,N-dimethyl lactamide (5.1 g, 43.5 mmol; obtained as described in Larcheveque M., Synthesis 1986, 1, 60) in DCM (300 ml). The mixture was stirred at room temperature for one hour. After evaporation of the solvents under vacuum, the residue was diluted with 6N methanolic ammonia (100 ml). The mixture was stirred at room temperature for 18 hours. After evaporation of the solvents, the residue was triturated in ether. The resulting solid was filtered and purified further by chromatography on silica gel (eluant: 3 to 5% methanol in DCM) to give (2R)—N,N-dimethyl-2-[(4-oxo-3,4-dihydroquinazolin-5-yl)oxy]propanamide as a white solid (5.4 g, 71%); NMR Spectrum (CDCl3) 1.77 (d, 3H), 2.94 (s, 3H), 3.19 (s, 3H), 5.10 (q, 1H), 6.92 (d, 1H), 7.35 (d, 1H), 7.63 (t, 1H), 8.00 (s, 1H); Mass spectrum MH+ 262.

Workup

  1. customAfter evaporation of the solvents under vacuum
  2. additionthe residue was diluted with 6N methanolic ammonia (100 ml)
  3. stirringThe mixture was stirred at room temperature for 18 hours
  4. customAfter evaporation of the solvents
  5. customthe residue was triturated in ether
  6. filtrationThe resulting solid was filtered
  7. custompurified further by chromatography on silica gel (eluant: 3 to 5% methanol in DCM)

Sources & evidence

ORD record
ord-a8eac9c1249849388ce7441a3e6b4d60
Source dataset
uspto-grants-2010_10
Patent number
US07820683B2

Reaction notes

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