Trifluoroacetic acid → 5,7-difluoro-3-methyl-N-(5-morpholinopyridin-3-yl)-2-(piperazin-1-yl)quinolin-4-amine

HRID 1431627Notes

Reaction equation

[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[C:4]([NH:27][C:28]1[CH:29]=[N:30][CH:31]=[C:32]([N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)[CH:33]=1)=[C:5]([CH3:26])[C:6]([N:13]1[CH2:18][CH2:17][N:16](C(OC(C)(C)C)=O)[CH2:15][CH2:14]1)=[N:7]2.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[C:4]([NH:27][C:28]1[CH:29]=[N:30][CH:31]=[C:32]([N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)[CH:33]=1)=[C:5]([CH3:26])[C:6]([N:13]1[CH2:14][CH2:15][NH:16][CH2:17][CH2:18]1)=[N:7]2

Participants

Conditions

Temperature: 0 °C

Procedure

The tert-butyl 4-(5,7-difluoro-3-methyl-4-(5-morpholinopyridin-3-ylamino)-quinolin-2-yl)piperazine-1-carboxylate (32 mg, 0.059 mmol) was dissolved in DCM (1.0 mL) and cooled to 0° C. The trifluoroacetic acid (1.00 mL, 13.0 mmol) was then added and the reaction mixture was allowed to slowly warm to rt over a period of 1 h. The reaction was then cond to dryness. The crude TFA salt was treated with satd sodium bicarbonate solution. The organic layer was dried over sodium sulfate and the filtrate was cond to give 5,7-difluoro-3-methyl-N-(5-morpholinopyridin-3-yl)-2-(piperazin-1-yl)quinolin-4-amine. 1H NMR (CDCl3) δ ppm 7.85 (1H, d, J=2.5 Hz), 7.63 (1H, d, J=2.2 Hz), 7.23 (1H, ddd, J=10.2, 2.5, 1.4 Hz), 6.79 (1H, d, J=12.9 Hz), 6.71 (1H, ddd, J=13.9, 8.8, 2.5 Hz), 6.49 (1H, t, J=2.3 Hz), 3.70-3.83 (4H, m), 3.19-3.32 (4H, m), 3.03-3.12 (4H, m), 2.92-3.03 (4H, m), 2.00 (3H, s). Mass Spectrum (ESI) m/e=441.2 (M+1).

Workup

temperatureto slowly warm to rt over a period of 1 h
dry with materialThe organic layer was dried over sodium sulfate

Sources & evidence

ORD record: ord-a8b866f9868e49b9a6fa252a67bfd473
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940724B2

Reaction notes

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