Acetic Acid → N-{3-[1-(4-Chloro-3-ethoxy-benzyl)-piperidin-4-ylamino]-phenyl}-acetamide

HRID 913069Notes

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.[Cl:31][C:32]1[CH:39]=[CH:38][C:35]([CH:36]=O)=[CH:34][C:33]=1[O:40][CH2:41][CH3:42].C([BH3-])#N.[Na+]>C(O)C>[Cl:31][C:32]1[CH:39]=[CH:38][C:35]([CH2:36][N:3]2[CH2:4][CH2:5][CH:6]([NH:9][C:10]3[CH:11]=[C:12]([NH:16][C:17](=[O:19])[CH3:18])[CH:13]=[CH:14][CH:15]=3)[CH2:7][CH2:8]2)=[CH:34][C:33]=1[O:40][CH2:41][CH3:42]

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 4-chloro-3-ethoxy-benzaldehyde (46.1 mg, 0.25 mmol, 1.25 equiv; intermediate E2, 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 10.0 mg (12%) of the title compound. MS (ISP): 402.3 [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-19cd267097e24998868990e89a31b09b
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026255B2

Reaction notes

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