p-Toluenesulfonic acid monohydrate → 2-(3,5-Dimethyl-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-5,7-difluoroquinazolin-4(3H)-one

HRID 591770ノート

反応式

HRID 591770 の反応式
[NH2:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]([F:12])[C:3]=1[C:4]([NH2:6])=[O:5].[CH3:13][C:14]1[CH:15]=[C:16]([CH:19]=[C:20]([CH3:30])[C:21]=1[O:22][CH2:23][CH2:24][N:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1)[CH:17]=O.S([O-])(O)=O.[Na+].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C>[CH3:30][C:20]1[CH:19]=[C:16]([C:17]2[NH:6][C:4](=[O:5])[C:3]3[C:2](=[CH:10][C:9]([F:11])=[CH:8][C:7]=3[F:12])[N:1]=2)[CH:15]=[C:14]([CH3:13])[C:21]=1[O:22][CH2:23][CH2:24][N:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1

参加物

6

反応物 4

HCID 521998p-Toluenesulfonic acid monohydrateHCID 23665763Sodium BisulfiteHCID 289325703,5-Dimethyl-4-(2-pyrrolidin-1-yl-ethoxy)-benzaldehydeHCID 594419592-Amino-4,6-difluorobenzamide

生成物 1

HCID 1363480212-(3,5-Dimethyl-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-5,7-difluoroquinazolin-4(3H)-one

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

反応条件

温度
145 °C

実験手順

To a solution of 2-amino-4,6-difluoro-benzamide (0.80 g, 4.60 mmol) and 3,5-dimethyl-4-(2-pyrrolidin-1-yl-ethoxy)-benzaldehyde (1.14 g, 4.60 mmol) in N,N-dimethylacetamide (60 mL) were added sodium hydrogen sulfite (58.5 wt %, 1.25 g, 6.9 mmol) and p-toluenesulfonic acid monohydrate (3.50 g, 18.4 mmol). The reaction mixture was stirred at 145° C. for 16 hours under nitrogen atmosphere, then cooled to room temperature. Solvent was evaporated under reduced pressure. Water (50 mL) was added, followed by saturated aqueous sodium bicarbonate solution (15 mL). The mixture was extracted with CH2Cl2 (2×100 mL) and washed with water. The organic phase was evaporated and the residue was washed with hexane/ether (90:10, 100 mL). The solid was filtered and dried under vacuum to give the title compound as a brown solid. Yield: 1.48 g (80%). MP 234-235° C. 1H NMR (400 MHz, DMSO-d6): δ 12.36 (s, 1H), 7.90 (s, 1H), 7.32 (m, 2H), 3.91 (t, J=4 Hz, 2H), 2.83 (t, J=4 Hz, 2H), 2.55 (s, 4H), 2.31 (s, 6H), 1.70 (s, 4H).

後処理

  1. temperaturecooled to room temperature
  2. customSolvent was evaporated under reduced pressure
  3. additionWater (50 mL) was added
  4. extractionThe mixture was extracted with CH2Cl2 (2×100 mL)
  5. washwashed with water
  6. customThe organic phase was evaporated
  7. washthe residue was washed with hexane/ether (90:10, 100 mL)
  8. filtrationThe solid was filtered
  9. customdried under vacuum

出典と根拠

ORDレコード
ord-e82d4e8abc30492e92eb20ed647db7d6
出典データセット
uspto-grants-2016_01
特許番号
US09238640B2

反応ノート

読み込み中…