Cesium carbonate → [2-Amino-6-[(4-methylpiperazin-1-yl)methyl]quinazolin-4-yl]-isoindolin-2-ylmethanone

HRID 1400167Notes

Reaction equation

HRID 1400167 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.[B-](F)(F)(F)[CH2:25][N:26]1[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]1.[K+].C(C1C=C(C(C)C)C=C(C(C)C)C=1P(C1CCCCC1)C1CCCCC1)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.C([O-])(=O)C.C([O-])(=O)C.[Pd+2].O>[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]([CH2:25][N:26]3[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]3)[CH:8]=2)[N:3]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 9801140Dicyclohexyl(2,4,6-triisopropylphenyl)phosphineHCID 45588174Potassium trifluoro[(4-methylpiperazin-1-yl)methyl]borate(1-)HCID 58457195(2-Amino-6-iodoquinazolin-4-yl)isoindolin-2-ylmethanone

Product 1

HCID 52939797[2-Amino-6-[(4-methylpiperazin-1-yl)methyl]quinazolin-4-yl]-isoindolin-2-ylmethanone

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

75 mg of (2-amino-6-iodoquinazolin-4-yl)isoindolin-2-ylmethanone are suspended in 2 ml of tetrahydrofuran and 7 μl of water together with 40 mg of potassium 1-methyl-4-trifluoroboratomethylpiperazine, 1 mg of palladium diacetate, 4 mg of ((2,4,6 triisopropyl)phenyl)dicyclohexylphosphine and 176 mg of caesium carbonate, and the mixture is stirred at 80° C. for 48 h. After cooling, the mixture is filtered through kieselguhr, rinsed three times with 5 ml of tetrahydrofuran each time, and the filtrate is evaporated to dry ness in vacuo. The residue is purified by means of preparative HPLC, and the title compound is isolated.

Workup

  1. temperatureAfter cooling
  2. filtrationthe mixture is filtered through kieselguhr
  3. washrinsed three times with 5 ml of tetrahydrofuran each time
  4. customthe filtrate is evaporated
  5. customto dry ness in vacuo
  6. customThe residue is purified by means of preparative HPLC

Sources & evidence

ORD record
ord-07ef5567ee444f72a1f3fa442e2dd120
Source dataset
uspto-grants-2014_12
Patent number
US08906930B2

Reaction notes

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