Water → 2-[2-Amino-4-(isoindoline-2-carbonyl)quinazolin-6-yl]-4-fluorobenzaldehyde

HRID 1631104Notes

Reaction equation

HRID 1631104 reaction equation
Br[C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].C(=O)([O-])[O-].[K+].[K+].O.[NH2:18][C:19]1[N:28]=[C:27]([C:29]([N:31]2[CH2:39][C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[CH2:32]2)=[O:30])[C:26]2[C:21](=[CH:22][CH:23]=[C:24](B3OC(C)(C)C(C)(C)O3)[CH:25]=2)[N:20]=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]>[NH2:18][C:19]1[N:28]=[C:27]([C:29]([N:31]2[CH2:32][C:33]3[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:39]2)=[O:30])[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([C:2]3[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=3[CH:4]=[O:5])[CH:25]=2)[N:20]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27733192-Bromo-4-fluorobenzaldehydeHCID 58457219[2-Amino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone

Product 1

HCID 867625702-[2-Amino-4-(isoindoline-2-carbonyl)quinazolin-6-yl]-4-fluorobenzaldehyde

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

244 mg of 2-bromo-4-fluorobenzaldehyde, 0.35 g of potassium carbonate, 4 μl of water and 98 mg of [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride are added to a solution of 500 mg of [2-amino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone in 12 ml of ethanol under argon. The mixture is heated at 120° C. for 4 h; then allowed to cool, during which a precipitate deposits. The precipitate is filtered off, taken up in 10 ml of ethyl acetate and washed 3 times with 10 ml of water each time. After drying over sodium sulfate, the mixture is filtered off and evaporated to dryness in vacuo; yield: 495 mg (91%) of 2-[2-amino-4-(isoindoline-2-carbonyl)quinazolin-6-yl]-4-fluorobenzaldehyde; HPLC retention time: 1.73 min;

Workup

  1. temperatureto cool, during which a precipitate deposits
  2. filtrationThe precipitate is filtered off
  3. washwashed 3 times with 10 ml of water each time
  4. dry with materialAfter drying over sodium sulfate
  5. filtrationthe mixture is filtered off
  6. customevaporated to dryness in vacuo

Sources & evidence

ORD record
ord-d6f1bd01503a4835a5c210d89418a6ee
Source dataset
uspto-grants-2014_07
Patent number
US08791129B2

Reaction notes

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