Trifluoroacetic acid → (R)-5-cyclopropyl-N-(3-fluoro-4-(morpholin-2-yl)phenyl)pyrimidin-2-amine

HRID 2403335Notes

Reaction equation

[CH:1]1([C:4]2[CH:5]=[N:6][C:7]([NH:10][C:11]3[CH:16]=[CH:15][C:14]([C@H:17]4[O:22][CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18]4)=[C:13]([F:30])[CH:12]=3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1.FC(F)(F)C(O)=O.CCOC(C)=O>C(#N)C.O>[CH:1]1([C:4]2[CH:5]=[N:6][C:7]([NH:10][C:11]3[CH:16]=[CH:15][C:14]([C@H:17]4[O:22][CH2:21][CH2:20][NH:19][CH2:18]4)=[C:13]([F:30])[CH:12]=3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1

Participants

Conditions

Temperature: 80 °C

Procedure

To a stirred solution of (R)-tert-butyl 2-(4-(5-cyclopropylpyrimidin-2-ylamino)-2-fluorophenyl)morpholine-4-carboxylate (180 mg) in acetonitrile (2 ml) and water (6 ml) was added trifluoroacetic acid (335 μl). The reaction mixture was then capped and the mixture was shaken at 80° C. for 16 h. The reaction mixture was then cooled to room temperature and poured into EtOAc and washed with 4 M aq. NaOH. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash column chromatography (silica gel; gradient: CH2Cl2/MeOH/aq. NH3) to afford (R)-5-cyclopropyl-N-(3-fluoro-4-(morpholin-2-yl)phenyl)pyrimidin-2-amine (57 mg, xx %) as an off-white solid. MS (ISP): 315.2 ([M+H]+).

Workup

customThe reaction mixture was then capped
temperatureThe reaction mixture was then cooled to room temperature
washwashed with 4 M aq. NaOH
dry with materialThe organic layer was dried over Na2SO4
concentrationconcentrated in vacuo
customThe crude material was purified by flash column chromatography (silica gel; gradient: CH2Cl2/MeOH/aq. NH3)

Sources & evidence

ORD record: ord-42c44d67b6dc44af9fe689cb2b7f6735
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08802673B2

Reaction notes

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