Potassium Acetate → 3-[3-Amino-1-(4-fluoro-3-pyrimidin-5-ylphenyl)-1H-isoindol-1-yl]phenyl trifluoromethanesulfonate

HRID 2264777Notes

Reaction equation

HRID 2264777 reaction equation
[F:1][C:2]([F:32])([F:31])[S:3]([O:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]2([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[C:25](Br)[CH:24]=3)[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]([NH2:22])=[N:14]2)[CH:8]=1)(=[O:5])=[O:4].[N:33]1[CH:38]=[C:37](B(O)O)[CH:36]=[N:35][CH:34]=1.C([O-])(=O)C.[K+].COC=COC>ClCCl.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O>[F:1][C:2]([F:32])([F:31])[S:3]([O:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]2([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[C:25]([C:37]4[CH:38]=[N:33][CH:34]=[N:35][CH:36]=4)[CH:24]=3)[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]([NH2:22])=[N:14]2)[CH:8]=1)(=[O:5])=[O:4]

Participants

7

Reactant 4

HCID 517044Potassium AcetateHCID 5223901,2-DimethoxyetheneHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 595962683-(3-Amino-1-(3-bromo-4-fluorophenyl)-1H-isoindol-1-yl)phenyl trifluoromethanesulfonate

Product 1

HCID 248748653-[3-Amino-1-(4-fluoro-3-pyrimidin-5-ylphenyl)-1H-isoindol-1-yl]phenyl trifluoromethanesulfonateYield 37%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolvent

Procedure

3-(3-Amino-1-(3-bromo-4-fluorophenyl)-1H-isoindol-1-yl)phenyl trifluoromethane-sulfonate (Scheme #20, H, 0.083 g, 0.16 mmol), 5-pyrimidinylboronic acid (0.019 g, 0.16 mmol), potassium acetate (0.031 g, 0.31 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane (0.006 g, 7.84 μmol) and solvent (2 mL of a mixture of dimethoxyethene and water in a ratio of 4:1) was irradiated under argon atmosphere in a microwave at 130° C. for 20 minutes. When cooled to ambient temperature the mixture was partitioned between ethylacetate and water, the organic phase was dried over magnesium sulfate and evaporated. Purification by preparative HPLC afforded 0.031 g (37%) of the title compound. 1H NMR (CDCl3) δ 9.18 (s, 1 H), 8.86 (d, J=1.26 Hz, 2 H), 7.58-7.45 (m, 4 H), 7.43-7.31 (m, 4 H), 7.30-7.25 (m, 1 H), 7.19-7.10 (m, 2 H), 5.43 (br s, 2 H); MS (ES) m/z 529 [M+1]+.

Workup

  1. customwas partitioned between ethylacetate and water
  2. dry with materialthe organic phase was dried over magnesium sulfate
  3. customevaporated
  4. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-5c27961f69ab4d31adb49803c6c6e45a
Source dataset
uspto-grants-2010_12
Patent number
US07855213B2

Reaction notes

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