2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → N-(2,5-Difluoro-4-(((S)-3-methylmorpholino)methyl)phenyl)-5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine

HRID 1924022Notes

Reaction equation

Br[C:2]1[C:15]([F:16])=[CH:14][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][O:10][CH2:9][C@@H:8]2[CH3:13])=[C:4]([F:17])[CH:3]=1.[F:18][C:19]1[C:20]([C:26]2[N:30]([CH:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)[C:29]([CH3:37])=[N:28][CH:27]=2)=[N:21][C:22]([NH2:25])=[N:23][CH:24]=1.CC(C)([O-])C.[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CN(C=O)C>[F:16][C:15]1[CH:14]=[C:5]([CH2:6][N:7]2[CH2:12][CH2:11][O:10][CH2:9][C@@H:8]2[CH3:13])[C:4]([F:17])=[CH:3][C:2]=1[NH:25][C:22]1[N:21]=[C:20]([C:26]2[N:30]([CH:31]3[CH2:32][CH2:33][O:34][CH2:35][CH2:36]3)[C:29]([CH3:37])=[N:28][CH:27]=2)[C:19]([F:18])=[CH:24][N:23]=1

Participants

Conditions

Temperature: 120 °C

Procedure

(S)-4-(4-Bromo-2,5-difluorobenzyl)-3-methylmorpholine (430 mg, 1.40 mmol), 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (389 mg, 1.40 mmol) and potassium tert-butoxide (158 mg, 1.40 mmol) were mixed in dioxane (7 mL) and argon was bubbled through the mixture for 5 minutes. Pd2(dba)3 (154 mg, 0.17 mmol) and X-Phos (161 mg, 0.34 mmol) were added followed by DMF (1.75 mL) and the reaction mixture was heated in a microwave reactor at 120° C. for 40 minutes.

Workup

customargon was bubbled through the mixture for 5 minutes

Sources & evidence

ORD record: ord-b3421a3ce33f42b6b31d4bb53e8106c8
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08178529B2

Reaction notes

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