Sodium Carbonate → 4-{2-Amino-6-[2-(4,5,6,7-tetrahydro-1H-benzimidazol-2-yl)-4-morpholinyl]-4-pyrimidinyl}-2-fluorobenzonitrile

HRID 2367346Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH:10]([C:14]3[NH:18][C:17]4[CH2:19][CH2:20][CH2:21][CH2:22][C:16]=4[N:15]=3)[CH2:9]2)[N:5]=[C:4]([NH2:23])[N:3]=1.[F:24][C:25]1[CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:30]=[CH:29][C:26]=1[C:27]#[N:28].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:23][C:4]1[N:3]=[C:2]([C:31]2[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[C:25]([F:24])[CH:32]=2)[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH:10]([C:14]3[NH:18][C:17]4[CH2:19][CH2:20][CH2:21][CH2:22][C:16]=4[N:15]=3)[CH2:9]2)[N:5]=1

Participants

Conditions

Temperature: 140 °C

Procedure

A mixture of 4-chloro-6-[2-(4,5,6,7-tetrahydro-1H-benzimidazol-2-yl)-4-morpholinyl]-2-pyrimidinamine (208 mg, 0.623 mmol), 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (200 mg, 0.809 mmol), Na2CO3 (165 mg, 1.557 mmol) and Pd(PPh3)4 (72 mg, 0.062 mmol) in 1,4-dioxane (6 mL) and water (2 mL) was heated at 140° C. under microwave condition with stirring for 1 hour. The mixture was filtered, washed by EtOAc (150 mL), evaporated, and chromatographed (PE-EtOAc, 3:1) to afford the title compound (150 mg) as a yellow solid. LC-MS (ES) m/z=420 [M+H]+.

Workup

filtrationThe mixture was filtered
washwashed by EtOAc (150 mL)
customevaporated
customchromatographed (PE-EtOAc, 3:1)

Sources & evidence

ORD record: ord-a354726edde24c8ea431d7cb0e0c0404
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08697685B2

Reaction notes

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