Cesium carbonate → 4-(4-amino-6-{4-[4-(4-fluoro-3-methyl-phenyl)-1-(2-hydroxy-ethyl)-1H-imidazol-2-yl]-piperidin-1-yl}-pyrimidin-5-yl)-pyrazole-1-carboxylic acid tert-butyl ester

HRID 2284056Notes

Reaction equation

[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([N:8]2[CH2:13][CH2:12][CH:11]([C:14]3[N:15]([CH2:27][CH2:28][OH:29])[CH:16]=[C:17]([C:19]4[CH:24]=[CH:23][C:22]([F:25])=[C:21]([CH3:26])[CH:20]=4)[N:18]=3)[CH2:10][CH2:9]2)[C:3]=1Br.[C:31]([O:35][C:36]([N:38]1[CH:42]=[C:41](B2OC(C)(C)C(C)(C)O2)[CH:40]=[N:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32].C([O-])([O-])=O.[Cs+].[Cs+]>O>[NH2:1][C:2]1[C:3]([C:41]2[CH:40]=[N:39][N:38]([C:36]([O:35][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:37])[CH:42]=2)=[C:4]([N:8]2[CH2:13][CH2:12][CH:11]([C:14]3[N:15]([CH2:27][CH2:28][OH:29])[CH:16]=[C:17]([C:19]4[CH:24]=[CH:23][C:22]([F:25])=[C:21]([CH3:26])[CH:20]=4)[N:18]=3)[CH2:10][CH2:9]2)[N:5]=[CH:6][N:7]=1

Participants

Conditions

Temperature: 50 °C

Procedure

a mixture of 2-[2-[1-(6-amino-5-bromo-pyrimidin-4-yl)-piperidin-4-yl]-4-(4-fluoro-3-methyl-phenyl)-imidazol-1-yl]-ethanol (1333.00 mg; 2.80 mmol; 1.00 eq.), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazole-1-carboxylic acid tert-butyl ester (1237.31 mg; 4.21 mmol; 1.50 eq.), Cs2CO3 (548 mg, 1.68 mmol) in doxane 10 ml and water 1 ml, purged with argon, added Pd(0) (tBu3)2 (143 mg, 0.28 mmol) stirred at 50° C. for overnight. LC-MS showed desired as major product, removed off solvent, purified by prep HPLC (Basic), collected title compound 400 mg, 25.4%

Workup

custompurged with argon
additionadded Pd(0) (tBu3)2 (143 mg, 0.28 mmol)
customremoved off solvent
custompurified by prep HPLC (Basic)
customcollected title compound 400 mg, 25.4%

Sources & evidence

ORD record: ord-dfb6d8684943437b9e3c22ef025c0c9a
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09145392B2

Reaction notes

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