Dimethylformamide → cis-4-amino-5-chloro-N-[1-(cyanomethyl)-3-methoxy-4-piperidinyl]-2-methoxybenzamide

HRID 654170Notes

Reaction equation

[NH2:1][C:2]1[C:18]([Cl:19])=[CH:17][C:5]([C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][NH:12][CH2:11][C@H:10]2[O:15][CH3:16])=[O:7])=[C:4]([O:20][CH3:21])[CH:3]=1.CN(C)C=O.Cl[CH2:28][C:29]#[N:30]>C(N(CC)CC)C>[NH2:1][C:2]1[C:18]([Cl:19])=[CH:17][C:5]([C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][N:12]([CH2:28][C:29]#[N:30])[CH2:11][C@H:10]2[O:15][CH3:16])=[O:7])=[C:4]([O:20][CH3:21])[CH:3]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a stirred solution of 12.55 parts of cis-4-amino-5-chloro-2-methoxy-N-(3-methoxy-4-piperidinyl)benzamide in 180 parts of N,N-dimethylformamide were added 5.05 parts of N,N-diethylethanamine and 3.4 parts of 2-chloroacetonitrile. The whole was stirred for 18 hours at 50° C. The solvent was evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was triturated in 1,1'-oxybisethane. The product was filtered off and dried, yielding 12.21 parts (86.5%) of cis-4-amino-5-chloro-N-[1-(cyanomethyl)-3-methoxy-4-piperidinyl]-2-methoxybenzamide; mp. 130.4° C. (interm. 2).

Workup

customThe solvent was evaporated
customThe residue was purified by column chromatography over silica gel using
additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
customThe pure fractions were collected
customthe eluent was evaporated
customThe residue was triturated in 1,1'-oxybisethane
filtrationThe product was filtered off
customdried

Sources & evidence

ORD record: ord-076421d380bb4871b171336d410dbad6
Source dataset: uspto-grants-1992_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05130312

Reaction notes

Loading…