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

HRID 1162207ノート

反応式

HRID 1162207 の反応式
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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-a8eac9c1249849388ce7441a3e6b4d60
出典データセット
uspto-grants-2010_10
特許番号
US07820683B2

反応ノート

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