6-(4-(Trifluoromethyl)phenyl)pyridin-3-amine → Methyl 3-(4-(1-(6-(4-(trifluoromethyl)phenyl)pyridin-3-ylamino)butyl)benzamido)propanoate

HRID 1427523Notes

Reaction equation

[C:1]([C:6]1[CH:20]=[CH:19][C:9]([C:10]([NH:12][CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])=[O:11])=[CH:8][CH:7]=1)(=O)[CH2:2][CH2:3][CH3:4].[F:21][C:22]([F:37])([F:36])[C:23]1[CH:28]=[CH:27][C:26]([C:29]2[N:34]=[CH:33][C:32]([NH2:35])=[CH:31][CH:30]=2)=[CH:25][CH:24]=1.[B][B][B][B][B][B][B][B][B][B]>CO>[F:37][C:22]([F:21])([F:36])[C:23]1[CH:24]=[CH:25][C:26]([C:29]2[N:34]=[CH:33][C:32]([NH:35][CH:1]([C:6]3[CH:20]=[CH:19][C:9]([C:10]([NH:12][CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])=[O:11])=[CH:8][CH:7]=3)[CH2:2][CH2:3][CH3:4])=[CH:31][CH:30]=2)=[CH:27][CH:28]=1

Participants

Conditions

Temperature: 30 °C

Procedure

To a solution of methyl 3-(4-butyrylbenzamido)propanoate (128 mg, 0.46 mmol) and 6-(4-(trifluoromethyl)phenyl)pyridin-3-amine (100 mg, 0.42 mmol, prepared as in Example 2.7, Step B) in dry methanol (4.8 mL) was added decaborane (31 mg, 0.25 mmol). The resulting mixture was stirred at 30° C. overnight. The solvent was removed under reduced pressure and the residue was purified by preparative TLC to provide impure methyl 3-(4-(1-(6-(4-(trifluoromethyl)phenyl)pyridin-3-ylamino)butyl)benzamido)propanoate. This material was dissolved in THF (3 mL) and water (3 mL). Aqueous lithium hydroxide (1.00 mmol) was added. The resulting mixture was stirred at 20° C. for 1 h. The solvent was removed under reduced pressure. The residue dissolved in water and the solution brought to pH 3-4 by addition of 1N aqueous HCl. The mixture was extracted with dichloromethane (10 mL*2). The combined organic layers were concentrated. Purified by preparative HPLC (column: Phenomenex Gemini C18 250×21.2 mm×10 μm; modifier: 0.225% formic acid; gradient: 10 to 30% acetonitrile in water) to give 3-(4-(1-(6-(4-(trifluoromethyl)phenyl)pyridin-3-ylamino)butyl)benzamido)propanoic acid (20 mg) as a colorless solid. 1H NMR (400 MHz, CD3OD) δ 7.90-7.95 (m, 3H), 7.86-7.79 (m, 5H), 7.52 (d, J=8.0 Hz, 2H), 7.43-7.47 (m 1H), 4.57-4.60 (m, 1H), 3.60-3.64 (m, 2H), 2.62-2.65 (m, 2H), 1.94-1.96 (m, 1H), 1.82-1.86 (m, 1H), 1.57-1.43 (m, 2H), 1.01 (t, J=7.2 Hz, 3H). MS (M+1)=486.3.

Workup

customThe solvent was removed under reduced pressure
customthe residue was purified by preparative TLC

Sources & evidence

ORD record: ord-76ec7a52efa146079757fdb981a37c67
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08933104B2

Reaction notes

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