Cesium carbonate → HCID 118003584, compound

HRID 2200522Notes

Reaction equation

HRID 2200522 reaction equation
[C:1]([C:3]1[CH:4]=[N:5][N:6]([CH3:9])[C:7]=1[CH3:8])#[CH:2].[NH2:10][C:11]1[C:19]([C:20]([NH:22][C@H:23]([C:25]2[N:34]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[C:33](=[O:41])[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][C:31]=3Cl)[N:26]=2)[CH3:24])=[O:21])=[C:14]2[N:15]=[CH:16][CH:17]=[CH:18][N:13]2[N:12]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C(#N)CC.CC#N.CC#N.Cl[Pd]Cl>[NH2:10][C:11]1[C:19]([C:20]([NH:22][C@H:23]([C:25]2[N:34]([C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=3)[C:33](=[O:41])[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][C:31]=3[C:2]#[C:1][C:3]3[CH:4]=[N:5][N:6]([CH3:9])[C:7]=3[CH3:8])[N:26]=2)[CH3:24])=[O:21])=[C:14]2[N:15]=[CH:16][CH:17]=[CH:18][N:13]2[N:12]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 122992991H-Pyrazole, 4-ethynyl-1,5-dimethyl-2×HCID 89841957HCID 89841957, compound

Product 1

HCID 118003584HCID 118003584, compound

Reagents, catalysts & solvents 2

HCID 6093782Bis(acetonitrile)dichloropalladiumCatalystHCID 7854PropionitrileSolvent

Conditions

Temperature
95 °C

Procedure

Compound 88 was prepared in analogous fashion as compound 21 in example 9 except that 4-ethynyl-1,5-dimethyl-1H-pyrazole was used in place of 4-ethynyl-1-methyl-1H-pyrazole. A suspension of (S)-2-amino-N-(1-(5-chloro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (146 mg, 0.317 mmol), Cesium carbonate (198 mg, 0.608 mmol, 2 eq.), Dichlorobis(acetonitrile)palladium (II) (15 mg, 0.058 mmol, 0.2 eq.) and Xphos (87 mg, 0.182, 0.6 eq.) in propionitrile (2 mL) was bubbled with argon for 5 minutes. The mixture was charged with 4-ethynyl-1,5-dimethyl-1H-pyrazole (73 mg, 0.6 mmol, 2 eq.), heated to 95° C. and stirred for 2 hr. The resulting mixture was cooled to RT, partitioned between Ethyl acetate and water. The organic phase was separated, washed with saturated aqueous sodium chloride solution, dried with sodium sulfate and concentrated. The residue was purified with silica gel chromatography using a gradient of DCM and MeOH to afford (S)-2-amino-N-(1-(5-((1,5-dimethyl-1H-pyrazol-4-yl)ethynyl)-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide. ESI-MS m/z: 544.2 [M+H]+.

Workup

  1. customwas bubbled with argon for 5 minutes
  2. temperatureThe resulting mixture was cooled to RT
  3. custompartitioned between Ethyl acetate and water
  4. customThe organic phase was separated
  5. washwashed with saturated aqueous sodium chloride solution
  6. dry with materialdried with sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified with silica gel chromatography

Sources & evidence

ORD record
ord-89e85834aed04eddb125a7898b0204ba
Source dataset
uspto-grants-2016_06
Patent number
US09359365B2

Reaction notes

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