6-(Trifluoromethyl)pyridine-3-carboxaldehyde → 2-Cyclopentyl-N-{2,6-dimethyl-4-[(6-trifluoromethyl-pyridin-3-ylmethyl)-amino]-phenyl}-acetamide

HRID 1820154Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([NH:9][C:10](=[O:17])[CH2:11][CH:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)=[C:4]([CH3:18])[CH:3]=1.[F:19][C:20]([F:30])([F:29])[C:21]1[N:26]=[CH:25][C:24]([CH:27]=O)=[CH:23][CH:22]=1>C(#N)C>[CH:12]1([CH2:11][C:10]([NH:9][C:5]2[C:4]([CH3:18])=[CH:3][C:2]([NH:1][CH2:27][C:24]3[CH:25]=[N:26][C:21]([C:20]([F:30])([F:19])[F:29])=[CH:22][CH:23]=3)=[CH:7][C:6]=2[CH3:8])=[O:17])[CH2:16][CH2:15][CH2:14][CH2:13]1

Participants

Conditions

Temperature: 150 °C

Procedure

N-(4-Amino-2,6-dimethyl-phenyl)-2-cyclopentyl-acetamide (204 mg) and 6-trifluoromethyl-pyridine-3-carbaldehyde (163 mg) were dissolved in acetonitrile (3 mL) and heated to 150° C. for 10 minutes in a sealed microwave process vial. The reaction mixture was concentrated in vacuo, redissolved in methanol (5 mL) followed by addition of acetic acid (0.5 mL) and sodium cyanoborohydride (244 mg) and stirred at 25° C. for 16 hours. Aqueous sodium carbonate (10%, 25 mL) was added, and the product was collected by filtration to furnish 0.311 g (92% yield) of the title compound as a white solid. LC-MS (m/z) 406 (MH+); tR=2.90, (UV, ELSD) 98%, 99%. 1H NMR (500 MHz, DMSO-d6): 1.20 (m, 2H), 1.51 (m, 2H), 1.60 (m, 2H), 1.75 (m, 2H), 1.97 (s, 6H), 2.22 (m, 3H), 4.39 (d, 2H), 6.20 (t, 1H), 6.28 (s, 2H), 7.85 (d, 1H), 7.99 (d, 1H), 8.75 (s, 1H), 8.77 (s, 1H).

Workup

concentrationThe reaction mixture was concentrated in vacuo
dissolutionredissolved in methanol (5 mL)
additionfollowed by addition of acetic acid (0.5 mL) and sodium cyanoborohydride (244 mg)
additionAqueous sodium carbonate (10%, 25 mL) was added
filtrationthe product was collected by filtration

Sources & evidence

ORD record: ord-9159aa530fa14b4e88771ab3f96a8528
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07601870B2

Reaction notes

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