4-Fluorobenzylamine → 2-(4-Fluoro-benzylamino)-N-[3-(2-pyrrolidin-1-yl-ethoxy)-4-trifluoromethyl-phenyl]-nicotinamide

HRID 2211667Notes

Reaction equation

Cl[C:2]1[N:28]=[CH:27][CH:26]=[CH:25][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[C:9]([O:17][CH2:18][CH2:19][N:20]2[CH2:24][CH2:23][CH2:22][CH2:21]2)[CH:8]=1)=[O:5].CCN(C(C)C)C(C)C.[F:38][C:39]1[CH:46]=[CH:45][C:42]([CH2:43][NH2:44])=[CH:41][CH:40]=1>CCOCC>[F:38][C:39]1[CH:46]=[CH:45][C:42]([CH2:43][NH:44][C:2]2[N:28]=[CH:27][CH:26]=[CH:25][C:3]=2[C:4]([NH:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[C:9]([O:17][CH2:18][CH2:19][N:20]3[CH2:24][CH2:23][CH2:22][CH2:21]3)[CH:8]=2)=[O:5])=[CH:41][CH:40]=1

Participants

Conditions

Temperature: 130 °C

Procedure

2-Chloro-N-[3-(2-pyrrolidin-1-yl-ethoxy)-4-trifluoromethyl-phenyl]-nicotinamide (199.1 mg), DIEA (252 μL) and 4-fluorobenzylamine (193 μL) were combined in a sealed tube and heated to 130° C. for 2 h. The mixture was purified on silica gel chromatography (2-3.5% MeOH/CH2Cl2). The desired fractions were concentrated in vacuo, and the residue was dissolved in Et2O and hexanes were added until the solution became cloudy. The solids were filtered, and dried. Additional material was obtained from the filtrate upon additional rounds of concentration, dissolving in Et2O and treatment with hexanes. M+H 503.4, Calc'd for C26H26N4O2F4-502.2.

Workup

customThe mixture was purified on silica gel chromatography (2-3.5% MeOH/CH2Cl2)
concentrationThe desired fractions were concentrated in vacuo
dissolutionthe residue was dissolved in Et2O
additionhexanes were added until the solution
filtrationThe solids were filtered
customdried
customAdditional material was obtained from the filtrate upon additional rounds of concentration

Sources & evidence

ORD record: ord-8609d89a78df4d209957136985cb35c5
Source dataset: uspto-grants-2006_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07101868B2

Reaction notes

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