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

HRID 1631103Notes

Reaction equation

HRID 1631103 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.[F:24][C:25]1[CH:26]=[CH:27][C:28]([CH2:34][OH:35])=[C:29](B(O)O)[CH:30]=1.C(=O)([O-])[O-].[K+].[K+].O>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]>[NH2:1][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:26]=[C:25]([F:24])[CH:30]=[CH:29][C:28]=3[CH2:34][OH:35])[CH:8]=2)[N:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 467397445-Fluoro-2-(hydroxymethyl)benzeneboronic acidHCID 58457195(2-Amino-6-iodoquinazolin-4-yl)isoindolin-2-ylmethanone

Product 1

HCID 56943415[2-Amino-6-[5-fluoro-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 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

10.405 g of (2-amino-6-iodoquinazolin-4-yl)-(1,3-dihydroisoindol-2-yl)methanone are dissolved in 450 ml of ethanol. 5 g of 5-fluoro-2-hydroxymethylphenylboronic acid, 10.4 g of potassium carbonate, 1 g of [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride and 450 μl of water are added to this solution, and the mixture is heated at 100° C. under argon for 1 h. The hot mixture is filtered off through Celite, and the filter cake is rinsed with 500 ml of hot ethanol. The filtrate is evaporated to dryness in vacuo, and the reddish residue obtained is triturated with 50 ml of acetonitrile, during which a beige solid precipitates out. This is filtered, washed with 20 ml of acetonitrile and dried at 40° C. in a drying cabinet for 16 h

Workup

  1. filtrationThe hot mixture is filtered off through Celite
  2. washthe filter cake is rinsed with 500 ml of hot ethanol
  3. customThe filtrate is evaporated to dryness in vacuo
  4. customthe reddish residue obtained
  5. customis triturated with 50 ml of acetonitrile, during which a beige solid
  6. customprecipitates out
  7. filtrationThis is filtered
  8. washwashed with 20 ml of acetonitrile
  9. customdried at 40° C. in a drying cabinet for 16 h

Sources & evidence

ORD record
ord-b1a85cb1403c48e6b78037e029a07358
Source dataset
uspto-grants-2014_07
Patent number
US08791129B2

Reaction notes

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