Acetic Acid → N-{3-[1-(3,5-Diethoxy-4-fluoro-benzyl)-piperidin-4-ylamino]-phenyl}-acetamide

HRID 2355541Notes

Reaction equation

Cl.Cl.[NH:3]1[CH2:8][CH2:7][CH:6]([NH:9][C:10]2[CH:11]=[C:12]([NH:16][C:17](=[O:19])[CH3:18])[CH:13]=[CH:14][CH:15]=2)[CH2:5][CH2:4]1.C(O)(=O)C.C(N(CC)CC)C.[CH2:31]([O:33][C:34]1[CH:35]=[C:36]([CH:39]=[C:40]([O:43][CH2:44][CH3:45])[C:41]=1[F:42])[CH:37]=O)[CH3:32].C([BH3-])#N.[Na+]>C(O)C>[CH2:31]([O:33][C:34]1[CH:35]=[C:36]([CH:39]=[C:40]([O:43][CH2:44][CH3:45])[C:41]=1[F:42])[CH2:37][N:3]1[CH2:4][CH2:5][CH:6]([NH:9][C:10]2[CH:11]=[C:12]([NH:16][C:17](=[O:19])[CH3:18])[CH:13]=[CH:14][CH:15]=2)[CH2:7][CH2:8]1)[CH3:32]

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of N-[3-(piperidin-4-ylamino)-phenyl]-acetamide dihydrochloride (61.2 mg, 0.2 mmol, 1.0 equiv; intermediate B1), acetic acid (60.1 mg, 1.0 mmol, 5.0 equiv) and triethylamine (40.5 mg, 0.4 mmol, 2.0 equiv) in ethanol (1 mL) was added 3,5-diethoxy-4-fluoro-benzaldehyde (53.1 mg, 0.25 mmol, 1.25 equiv; intermediate E5, vide infra) and the mixture stirred at 50° C. After 1 h, sodium cyanoborohydride (15.1 mg, 0.24 mmol, 1.2 equiv), dissolved in ethanol (1 mL), was added and the mixture stirred at 50° C. over night. Removal of the solvent under reduced pressure and purification by preparative HPLC on reversed phase eluting with a gradient of acetonitrile/water provided 19.9 mg (23%) of the title compound. MS (ISP): 430.4 [M+H]+.

Workup

additionwas added
stirringthe mixture stirred at 50° C. over night
customRemoval of the solvent
customunder reduced pressure and purification by preparative HPLC on reversed phase
washeluting with a gradient of acetonitrile/water

Sources & evidence

ORD record: ord-a7ee94e2f0ee43f1bd6a8db8f695f7a3
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07754744B2

Reaction notes

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