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

HRID 2407017Notes

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, StepB) 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 underreduced 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-7a6481aeebda45278a6a6b7e461c27ab
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08809342B2

Reaction notes

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