Water → [2-Amino-6-[2-(hydroxymethyl)phenyl]quinazolin-4-yl]isoindolin-2-ylmethanone

HRID 1631102Notes

Reaction equation

HRID 1631102 reaction equation
[NH2:1][C:2]1[N:11]=[C:10]([C:12]([N:14]2[CH2:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15]2)=[O:13])[C:9]2[C:4](=[CH:5][CH:6]=[C:7](I)[CH:8]=2)[N:3]=1.[OH:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].O>COCCOC.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]>[NH2:1][C:2]1[N:11]=[C:10]([C:12]([N:14]2[CH2:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15]2)=[O:13])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=3[CH2:25][OH:24])[CH:8]=2)[N:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 43742622-(Hydroxymethyl)phenylboronic AcidHCID 58457195(2-Amino-6-iodoquinazolin-4-yl)isoindolin-2-ylmethanone

Product 1

HCID 56943443[2-Amino-6-[2-(hydroxymethyl)phenyl]quinazolin-4-yl]isoindolin-2-ylmethanone

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
130 °C

Procedure

100 mg of (2-amino-6-iodoquinazolin-4-yl)-(1,3-dihydroisoindol-2-yl)methanone are dissolved in 2 ml of ethylene glycol dimethyl ether. 48 mg of 2-hydroxymethylphenylboronic acid, 66 mg of potassium carbonate, 14 mg of [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride and 50 μl of water are added to this solution, and the mixture is heated at 130° C. under argon for 30 min. The hot mixture is filtered off through Celite, and the solution is evaporated to dryness under reduced pressure. The reddish residue obtained is triturated with acetonitrile, during which a beige solid precipitates out. This is filtered, washed with acetonitrile and dried overnight at 40° C. in a drying cabinet.

Workup

  1. filtrationThe hot mixture is filtered off through Celite
  2. customthe solution is evaporated to dryness under reduced pressure
  3. customThe reddish residue obtained
  4. customis triturated with acetonitrile, during which a beige solid
  5. customprecipitates out
  6. filtrationThis is filtered
  7. washwashed with acetonitrile
  8. customdried overnight at 40° C. in a drying cabinet

Sources & evidence

ORD record
ord-9d9d96fadb784e3c8e0e917edd1a3463
Source dataset
uspto-grants-2014_07
Patent number
US08791129B2

Reaction notes

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