Cesium carbonate → 4-(4-Chloro-5-(2,5-dimethyl-7-(pentan-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)thiazol-2-yl)morpholine

HRID 1660748Notes

Reaction equation

[CH2:1]([CH:3]([C:6]1[N:11]2[N:12]=[C:13]([CH3:16])[C:14](I)=[C:10]2[N:9]=[C:8]([CH3:17])[CH:7]=1)[CH2:4][CH3:5])[CH3:2].[Cl:18][C:19]1[N:20]=[C:21]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[S:22][CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C)C=O.[Cu](I)I.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:18][C:19]1[N:20]=[C:21]([N:24]2[CH2:25][CH2:26][O:27][CH2:28][CH2:29]2)[S:22][C:23]=1[C:14]1[C:13]([CH3:16])=[N:12][N:11]2[C:6]([CH:3]([CH2:4][CH3:5])[CH2:1][CH3:2])=[CH:7][C:8]([CH3:17])=[N:9][C:10]=12

Participants

Conditions

Temperature: 125 °C

Procedure

Combine 7-(1-ethyl-propyl)-3-iodo-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine, (9 g, 26.2 mmol) and 4-chloro-2-morpholino-thiazole (7.5 g, 36 7 mmol) in dimethylformamide (90 mL) previously degassed with nitrogen. Add cesium carbonate (17.8 g, 55 mmol), copper iodide (250 mg, 1.31 mmol), triphenylphosphine (550 mg, 2.09 mmol) and palladium acetate (117 mg, 0.52 mmol). Heat the mixture to 125° C. for 16 h and then cool to 22° C. Add water (900 mL) and extract with methyl-t-butyl ether (3×200 mL). Combine the organic portions and evaporate the solvent. Purify by silica gel chromatography eluting with hexanes/ethyl acetate (4/1) to afford the title compound (6.4 g, 62%). ES/MS m/z (35Cl) 420 (M+1)+.

Workup

temperaturecool to 22° C
extractionAdd water (900 mL) and extract with methyl-t-butyl ether (3×200 mL)
customCombine the organic portions and evaporate the solvent
customPurify by silica gel chromatography
washeluting with hexanes/ethyl acetate (4/1)

Sources & evidence

ORD record: ord-cd92367400424b2d8aced9ed38de037d
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08030304B2

Reaction notes

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