Acetic Acid → (3R)-3-ethyl-1-(2-((4-(4-(hydroxymethyl)tetrahydro-2H-pyran-4-yl)phenyl)amino)pyrimidin-4-yl)-2-oxopyrrolidine-3-carbonitrile

HRID 714880Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:12][CH2:11][C@:10]([CH2:15][CH3:16])([C:13]#[N:14])[C:9]2=[O:17])[CH:5]=[CH:4][N:3]=1.[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2([CH2:31][OH:32])[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)=[CH:21][CH:20]=1.C(O)(=O)C>C(O)C>[CH2:15]([C@:10]1([C:13]#[N:14])[CH2:11][CH2:12][N:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]4([CH2:31][OH:32])[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[CH:21][CH:20]=3)[N:7]=2)[C:9]1=[O:17])[CH3:16]

Participants

Conditions

Temperature: 150 °C

Procedure

To a solution of (3R)-1-(2-chloropyrimidin-4-yl)-3-ethyl-2-oxopyrrolidine-3-carbonitrile (100 mg) obtained in Step A of Example 8 in ethanol (3.0 mL) were added (4-(4-aminophenyl)tetrahydro-2H-pyran-4-yl)methanol (83 mg) obtained in Step B of Example 152 and acetic acid (25 μL), and the mixture was stirred in a microwave reactor at 150° C. for 1 hr. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate), and recrystallized (hexane/ethyl acetate) to give the title compound (100 mg).

Workup

concentrationThe reaction mixture was concentrated under reduced pressure
customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate)
customrecrystallized (hexane/ethyl acetate)

Sources & evidence

ORD record: ord-820605b3c986422297080c00692b8bce
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09187453B2

Reaction notes

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