Water → [2-Amino-6-[4,5-difluoro-2-(hydroxymethyl)phenyl]quinazolin-4-yl]isoindolin-2-ylmethanone

HRID 1631109Notes

Reaction equation

Br[C:2]1[CH:7]=[C:6]([F:8])[C:5]([F:9])=[CH:4][C:3]=1[CH2:10][OH:11].C(=O)([O-])[O-].[K+].[K+].O.[NH2:19][C:20]1[N:29]=[C:28]([C:30]([N:32]2[CH2:40][C:39]3[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=3)[CH2:33]2)=[O:31])[C:27]2[C:22](=[CH:23][CH:24]=[C:25](B3OC(C)(C)C(C)(C)O3)[CH:26]=2)[N:21]=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]>[NH2:19][C:20]1[N:29]=[C:28]([C:30]([N:32]2[CH2:33][C:34]3[C:39](=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH2:40]2)=[O:31])[C:27]2[C:22](=[CH:23][CH:24]=[C:25]([C:2]3[CH:7]=[C:6]([F:8])[C:5]([F:9])=[CH:4][C:3]=3[CH2:10][OH:11])[CH:26]=2)[N:21]=1

Participants

Conditions

Temperature: 120 °C

Procedure

43 mg of (2-bromo-4,5-difluorophenyl)methanol, 80 mg of potassium carbonate, 4 μl of water and 16 mg of [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride are added to a solution of 100 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 10 ml of ethanol under argon. The mixture is heated at 120° C. for 30 min; during which a precipitate forms. After cooling to 22° C., 10 ml of water are added, and the precipitate is filtered off. The residue is washed 3 times with 25 ml of ethanol each time and dried at 40° C. in vacuo.

Workup

temperatureAfter cooling to 22° C.
filtrationthe precipitate is filtered off
washThe residue is washed 3 times with 25 ml of ethanol each time
customdried at 40° C. in vacuo

Sources & evidence

ORD record: ord-5c88f3c3e7ee4d59b76aa4a907b18448
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08791129B2

Reaction notes

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