Diisopropylethylamine → 4-[(3-Chloro-4-fluorophenyl)amino]-6-[(3-ethoxycarbonyl-1-oxo-2-propen-1-yl)-amino]-7-cyclopropylmethoxy-quinazoline

HRID 488412노트

반응식

HRID 488412 반응식
Cl[C:2]([CH:4]=[CH:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])=[O:3].[NH2:11][C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][C:21]=1[O:22][CH2:23][CH:24]1[CH2:26][CH2:25]1)[N:18]=[CH:17][N:16]=[C:15]2[NH:27][C:28]1[CH:33]=[CH:32][C:31]([F:34])=[C:30]([Cl:35])[CH:29]=1.C(N(C(C)C)CC)(C)C>O1CCCC1>[Cl:35][C:30]1[CH:29]=[C:28]([NH:27][C:15]2[C:14]3[C:19](=[CH:20][C:21]([O:22][CH2:23][CH:24]4[CH2:25][CH2:26]4)=[C:12]([NH:11][C:2](=[O:3])[CH:4]=[CH:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH:13]=3)[N:18]=[CH:17][N:16]=2)[CH:33]=[CH:32][C:31]=1[F:34]

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 155418526-Amino-4-[(3-chloro-4-fluorophenyl)amino]-7-cyclopropylmethoxyquinazolineHCID 53401111Ethyl 4-chloro-4-oxobut-2-enoate

생성물 1

HCID 698057484-[(3-Chloro-4-fluorophenyl)amino]-6-[(3-ethoxycarbonyl-1-oxo-2-propen-1-yl)-amino]-7-cyclopropylmethoxy-quinazoline

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

A solution of 3.00 g of ethyl 3-chlorocarbonyl-acrylate in 50 ml of tetrahydrofuran is added dropwise to 5.00 g of 6-amino-4-[(3-chloro-4-fluorophenyl)amino]-7-cyclopropylmethoxy-quinazoline and 3.5 ml of diisopropylethylamine in 150 ml of tetrahydrofuran while cooling with an ice bath. The reaction mixture is stirred for a further hour while cooling with an ice bath and then stirred overnight at ambient temperature. Next, the solvent is largely distilled off in the rotary evaporator and the residue is partitioned between water and ethyl acetate. The organic phase is washed with saturated sodium chloride solution, dried over magnesium sulphate and concentrated by evaporation. The brown, oily crude product is stirred with diethylether, the precipitate formed is suction filtered and washed with a little diethylether. Yield: 3.20 g (47% of theory), Rf value: 0.80 (silica gel, ethyl acetate) Mass spectrum (ESI*): m/z=485, 487 [M+]*

후처리

  1. temperaturewhile cooling with an ice bath
  2. temperaturewhile cooling with an ice bath
  3. stirringstirred overnight at ambient temperature
  4. distillationNext, the solvent is largely distilled off in the rotary evaporator
  5. customthe residue is partitioned between water and ethyl acetate
  6. washThe organic phase is washed with saturated sodium chloride solution
  7. dry with materialdried over magnesium sulphate
  8. concentrationconcentrated by evaporation
  9. stirringThe brown, oily crude product is stirred with diethylether
  10. customthe precipitate formed
  11. filtrationfiltered
  12. washwashed with a little diethylether

출처 및 근거

ORD 기록
ord-2094a098413749ab821f75dcef6da8f8
출처 데이터셋
uspto-grants-2005_12
특허 번호
US06972288B1

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