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

HRID 591770노트

반응식

HRID 591770 반응식
[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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

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온도
145 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-e82d4e8abc30492e92eb20ed647db7d6
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09238640B2

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