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

HRID 2173879Notes

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 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-307977d7e65c44ee9e6bd8ec348645b8
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09056834B2

Reaction notes

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