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

HRID 1924021Notes

Reaction equation

[F:1][C:2]1[C:3]([C:9]2[N:13]([CH:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[C:12]([CH3:20])=[N:11][CH:10]=2)=[N:4][C:5]([NH2:8])=[N:6][CH:7]=1.[Cl:21][C:22]1[C:34]([F:35])=[CH:33][C:25]([CH2:26][N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)=[C:24]([F:36])[CH:23]=1.CC(C)([O-])C.[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>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]>[ClH:21].[F:35][C:34]1[CH:33]=[C:25]([CH2:26][N:27]2[CH2:28][CH2:29][O:30][CH2:31][CH2:32]2)[C:24]([F:36])=[CH:23][C:22]=1[NH:8][C:5]1[N:4]=[C:3]([C:9]2[N:13]([CH:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[C:12]([CH3:20])=[N:11][CH:10]=2)[C:2]([F:1])=[CH:7][N:6]=1

Participants

Conditions

Temperature: 102 °C

Procedure

5-Fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (432 mg, 1.56 mmol) was dissolved in 1,4-dioxane (18 ml) and 4-(4-chloro-2,5-difluorobenzyl)morpholine (390 mg, 1.57 mmol) and potassium tert-butoxide (230 mg, 2.05 mmol) were added. The mixture was flushed with argon and stirred for 5-10 minutes. Tris(dibenzylideneacetone)dipalladium(0) (144 mg, 0.16 mmol) and 2-dicyclohexylphosphino-2′,4′,6′-tri-iso-propyl-1,1′-biphenyl (150 mg, 0.31 mmol) were added. The mixture was heated at 102° C. under an atmosphere of argon for 3 h.

Workup

customThe mixture was flushed with argon

Sources & evidence

ORD record: ord-bc89d725b59e48e99e2aa2efbb346b91
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08178529B2

Reaction notes

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