Tricyclohexylphosphine → 5-Cyclopropyl-6-(4-(1-(2-(dimethylamino)ethyl)-4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidin-1-yl)pyrimidin-4-amine

HRID 2284013Notes

Reaction equation

Br[C:2]1[C:3]([NH2:35])=[N:4][CH:5]=[N:6][C:7]=1[N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[N:15]([CH2:30][CH2:31][N:32]([CH3:34])[CH3:33])[CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[C:21]([C:26]([F:29])([F:28])[F:27])[CH:20]=3)[N:18]=2)[CH2:10][CH2:9]1.[CH:36]1(B2OC(C)(C)C(C)(C)O2)[CH2:38][CH2:37]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:36]1([C:2]2[C:3]([NH2:35])=[N:4][CH:5]=[N:6][C:7]=2[N:8]2[CH2:13][CH2:12][CH:11]([C:14]3[N:15]([CH2:30][CH2:31][N:32]([CH3:34])[CH3:33])[CH:16]=[C:17]([C:19]4[CH:24]=[CH:23][C:22]([F:25])=[C:21]([C:26]([F:29])([F:28])[F:27])[CH:20]=4)[N:18]=3)[CH2:10][CH2:9]2)[CH2:38][CH2:37]1

Participants

Conditions

Temperature: 100 °C

Procedure

In a microwave vial containing 5-bromo-6-{4-[1-(2-dimethylamino-ethyl)-4-(4-fluoro-3-trifluoromethyl-phenyl)-1H-imidazol-2-yl]-piperidin-1-yl}-pyrimidin-4-ylamine (70.00 mg; 0.13 mmol; 1.00 eq.) in Toluene (3.50 ml) and water (0.35 ml) was added 2-cyclopropyl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (0.09 ml; 0.50 mmol; 4.00 eq.), Palladium acetate (4.24 mg; 0.02 mmol; 0.15 eq.), Tricyclohexyl-phosphane (10.58 mg; 0.04 mmol; 0.30 eq.) and Potassium phosphonate (112.16 mg; 0.53 mmol; 4.20 eq.). The mixture was stirred at 100° C. for 5 h before the reaction mixture was filtered, concentrated and purified via waters pre-HPLC. LC-MS: (M+1=518, obsd.=518).

Workup

filtrationwas filtered
concentrationconcentrated
custompurified via waters pre-HPLC

Sources & evidence

ORD record: ord-a8a3619f25d3433088c00f7a9dfcecc3
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09145392B2

Reaction notes

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