Water → 2-[2-Amino-4-(1,3-dihydroisoindole-2-carbonyl)quinazolin-6-yl]benzoic acid

HRID 1887228노트

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HRID 1887228 반응식
CC1(C)C(C)(C)OB([C:9]2[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=2[C:11]([O:13]CC)=[O:12])O1.C(=O)([O-])[O-].[K+].[K+].O.[NH2:28][C:29]1[N:38]=[C:37]([C:39]([N:41]2[CH2:49][C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[CH2:42]2)=[O:40])[C:36]2[C:31](=[CH:32][CH:33]=[C:34](I)[CH:35]=2)[N:30]=1>C(O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:28][C:29]1[N:38]=[C:37]([C:39]([N:41]2[CH2:42][C:43]3[C:48](=[CH:47][CH:46]=[CH:45][CH:44]=3)[CH2:49]2)=[O:40])[C:36]2[C:31](=[CH:32][CH:33]=[C:34]([C:9]3[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=3[C:11]([OH:13])=[O:12])[CH:35]=2)[N:30]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 2773962Ethyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoateHCID 58457195(2-Amino-6-iodoquinazolin-4-yl)isoindolin-2-ylmethanone

생성물 1

HCID 584571912-[2-Amino-4-(1,3-dihydroisoindole-2-carbonyl)quinazolin-6-yl]benzoic acid

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 702Ethanol용매

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온도
120 °C

실험 절차

266 mg of ethyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate, 399 mg of potassium carbonate, 3 ml of water and 17.7 mg of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) are added to a solution of 300 mg of 2-amino-6-iodo-4-(1,3-dihydroisoindol-2-ylcarbonyl)quinazoline (“A130”) in 10 ml of ethanol under argon. The mixture is heated at 120° C. for 30 min, during which a clear solution forms. It is filtered through kieselguhr while hot. On cooling, ethyl 2-[2-amino-4-(1,3-dihydroisoindole-2-carbonyl)quinazolin-6-yl]benzoate crystallises out (retention time LC-MS: 2.056 min; “gradient polar” method). The crystals are taken up in 10 ml of sodium hydroxide solution (2 N) and stirred at 25° C. for 12 h. The mixture is extracted three times with 10 ml of diethyl ether each time, the aqueous phase is adjusted to pH 7, and the mixture is re-extracted with 10 ml of diethyl ether each time. The organic phase is dried over sodium sulfate and filtered, the filtrate is evaporated to dryness in vacuo.

후처리

  1. filtrationIt is filtered through kieselguhr while hot
  2. temperatureOn cooling
  3. customethyl 2-[2-amino-4-(1,3-dihydroisoindole-2-carbonyl)quinazolin-6-yl]benzoate crystallises out (retention time LC-MS: 2.056 min; “gradient polar” method)
  4. extractionThe mixture is extracted three times with 10 ml of diethyl ether each time
  5. extractionthe mixture is re-extracted with 10 ml of diethyl ether each time
  6. dry with materialThe organic phase is dried over sodium sulfate
  7. filtrationfiltered
  8. customthe filtrate is evaporated to dryness in vacuo

출처 및 근거

ORD 기록
ord-88d77be173724dda816f2c39916611d5
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08501754B2

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