Acetic Acid → (2-Chloro-pyrimidin-4-yl)-[1-(3-ethoxy-4-methyl-benzyl)-piperidin-4-yl]-amine

HRID 2242965Notes

Reaction equation

Cl.Cl.[Cl:3][C:4]1[N:9]=[C:8]([NH:10][CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)[CH:7]=[CH:6][N:5]=1.C(O)(=O)C.C(N(C(C)C)C(C)C)C.[CH2:30]([O:32][C:33]1[CH:34]=[C:35]([CH:38]=[CH:39][C:40]=1[CH3:41])[CH:36]=O)[CH3:31].C([BH3-])#N.[Na+]>C(O)C>[Cl:3][C:4]1[N:9]=[C:8]([NH:10][CH:11]2[CH2:16][CH2:15][N:14]([CH2:36][C:35]3[CH:38]=[CH:39][C:40]([CH3:41])=[C:33]([O:32][CH2:30][CH3:31])[CH:34]=3)[CH2:13][CH2:12]2)[CH:7]=[CH:6][N:5]=1

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of (2-chloro-pyrimidin-4-yl)-piperidin-4-yl-amine dihydrochloride (42.9 mg, 0.15 mmol, 1.0 equiv; intermediate C1) in ethanol (2 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 D10, 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 2.4 mg (4%) of the title compound. MS (ISP): 361.3 [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-ecd6f1c65166498b967f03e7296be0bb
Source dataset: uspto-grants-2010_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07674804B2

Reaction notes

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