Cesium carbonate → Trifluoroacetic acid

HRID 713352Notes

Reaction equation

[OH:1][C:2]([C:4]([F:7])([F:6])[F:5])=[O:3].[F:8][C:9]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:10]=1[O:11][CH:12]1[CH2:17][CH2:16][N:15]([C:18]2[N:23]=[C:22]3[CH2:24][NH:25][CH2:26][CH2:27][C:21]3=[N:20][C:19]=2[NH:28][CH:29]([CH3:31])[CH3:30])[CH2:14][CH2:13]1.C([O-])([O-])=O.[Cs+].[Cs+].FC(F)CI>CN(C=O)C>[F:5][CH:4]([F:7])[CH2:2][N:25]1[CH2:26][CH2:27][C:21]2[C:22](=[N:23][C:18]([N:15]3[CH2:16][CH2:17][CH:12]([O:11][C:10]4[CH:32]=[CH:33][C:34]([F:36])=[CH:35][C:9]=4[F:8])[CH2:13][CH2:14]3)=[C:19]([NH:28][CH:29]([CH3:31])[CH3:30])[N:20]=2)[CH2:24]1.[C:2]([OH:3])([C:4]([F:7])([F:6])[F:5])=[O:1]

Participants

Conditions

Temperature: 80 °C

Procedure

To a suspension of 3-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-N-isopropyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt (50 mg, 0.080 mmol) and Cs2CO3 (92 mg, 0.281 mmol) in DMF (0.5 mL) was added 1,1-difluoro-2-iodoethane (0.071 mL, 0.804 mmol) at 23° C. The reaction mixture was stirred at 80° C. for 18 h. The resulting crude material was filtered, rinsed with DMSO (2×0.5 mL), and purified by HPLC Method B using a 30% to 70% ACN gradient to give the title compound as a TFA salt (6.1 mg, 13%) as a yellow film. 1H NMR (500 MHz, DMSO-d6) δ ppm 1.19 (d, J=6.4 Hz, 6H), 1.82-1.93 (m, 2H), 2.03-2.10 (m, 2H), 2.79-2.98 (m, 4H), 3.24-3.32 (m, 2H), 3.33-3.75 (m, 4H), 4.05-4.18 (m, 3H), 4.52-4.55 (m, 1H), 5.76-5.82 (m, 1H), 6.39-6.72 (m, 1H), 7.00-7.04 (m, 1H), 7.25-7.34 (m, 2H); ESI-MS m/z [M+H]+ 468.3.

Workup

filtrationThe resulting crude material was filtered
washrinsed with DMSO (2×0.5 mL)
custompurified by HPLC Method B

Sources & evidence

ORD record: ord-63be07ed6a17406fa4a6b2fcd957aff1
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181249B2

Reaction notes

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