Acetic Acid → 4-(4-Chloro-benzoylamino)-1-(4-chloro-3-ethoxy-benzyl)-piperidine-4-carboxylic acid amide

HRID 913333Notes

Reaction equation

Cl.[Cl:2][C:3]1[CH:19]=[CH:18][C:6]([C:7]([NH:9][C:10]2([C:16]#[N:17])[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[O:8])=[CH:5][CH:4]=1.C(O)(=[O:22])C.C(N(C(C)C)C(C)C)C.[Cl:33][C:34]1[CH:41]=[CH:40][C:37]([CH:38]=O)=[CH:36][C:35]=1[O:42][CH2:43][CH3:44].C([BH3-])#N.[Na+]>C(O)C>[Cl:2][C:3]1[CH:19]=[CH:18][C:6]([C:7]([NH:9][C:10]2([C:16]([NH2:17])=[O:22])[CH2:11][CH2:12][N:13]([CH2:38][C:37]3[CH:40]=[CH:41][C:34]([Cl:33])=[C:35]([O:42][CH2:43][CH3:44])[CH:36]=3)[CH2:14][CH2:15]2)=[O:8])=[CH:5][CH:4]=1

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of 4-chloro-N-(4-cyano-piperidin-4-yl)-benzamide hydrochloride (45.03 mg, 0.15 mmol, 1.0 equiv) 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 4-chloro-3-ethoxy-benzaldehyde (33.2 mg, 0.18 mmol, 1.2 equiv; intermediate B1) 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 9.7 mg (14%) of the title compound. MS (ISP): 450.2 [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-b95d00cd1b9341268d78f7d25c2e97dd
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026365B2

Reaction notes

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