Acetic Acid → [1-(3-Ethoxy-4-methyl-benzyl)-piperidin-4-yl]-pyridin-3-yl-amine

HRID 547895Notes

Reaction equation

Cl.Cl.[NH:3]1[CH2:8][CH2:7][CH:6]([NH:9][C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[CH2:5][CH2:4]1.C(O)(=O)C.C(N(C(C)C)C(C)C)C.[CH2:29]([O:31][C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][C:39]=1[CH3:40])[CH:35]=O)[CH3:30].C([BH3-])#N.[Na+]>C(O)C>[CH2:29]([O:31][C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][C:39]=1[CH3:40])[CH2:35][N:3]1[CH2:8][CH2:7][CH:6]([NH:9][C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[CH2:5][CH2:4]1)[CH3:30]

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of piperidin-4-yl-pyridin-3-yl-amine dihydrochloride (37.5 mg, 0.15 mmol, 1.0 equiv; intermediate A1) in ethanol (1 mL), acetic acid (72.1 mg, 1.2 mmol, 8.0 equiv) and N-ethyl diisopropylamine (77.6 mg, 0.6 mmol, 4.0 equiv) was added 3-ethoxy-4-methyl-benzaldehyde (29.6 mg, 0.18 mmol, 1.2 equiv; intermediate B21, vide infra) and the mixture stirred at 55° C. After 1 h, sodium cyanoborohydride (47.1 mg, 0.75 mmol, 5.0 equiv), dissolved in ethanol (0.5 mL), was added and the mixture stirred at 55° 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 11.3 mg (23%) of the title compound. MS (ISP): 326.3 [M+H]+.

Workup

additionwas added
stirringthe mixture stirred at 55° 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-b27bb164f0644d79ad328209de320741
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07939661B2

Reaction notes

Loading…