Potassium Carbonate → (R)-(1-(2-(2-Cyclopropylpyrimidin-4-yl)-1H-imidazo[4,5-b]pyrazin-6-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone

HRID 931232Notes

Reaction equation

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

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 6-bromo-2-(2-cyclopropylpyrimidin-4-yl)-1H-imidazo[4,5-b]pyrazine (86 mg, 0.3 mmol), (R)-piperidin-3-yl(pyrrolidin-1-yl)methanone (95 mg, 0.4 mmol), potassium carbonate (98.4, 0.7 mmol), cesium fluoride (124 mg, 0.8 mmol) and diglyme (1.0 mL) was heated to 150° C. for 3 days. The mixture was diluted with water and aqueous hydrochloric acid (1N). The mixture was extracted with ethyl acetate (3×). The combined organics were washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified via HPLC to afford the title compound. MS (ESI+) (M+H) 419.3, HPLC retention time 2.44 min (Method A).

Workup

extractionThe mixture was extracted with ethyl acetate (3×)
washThe combined organics were washed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated under reduced pressure
customThe residue was purified via HPLC

Sources & evidence

ORD record: ord-bf44809cecea40d3ae4e5db7d3bdd3e7
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296745B2

Reaction notes

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