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

HRID 1887228Notes

Reaction equation

HRID 1887228 reaction equation
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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-88d77be173724dda816f2c39916611d5
Source dataset
uspto-grants-2013_08
Patent number
US08501754B2

Reaction notes

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