1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → N-(3-(trifluoromethyl)benzyl)-2-(2-(2-(chloromethyl)picolinamido)-5-(piperidin-1-yl)phenyl)isonicotinamide

HRID 625361Notes

Reaction equation

HRID 625361 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([CH:29]=[CH:30][CH:31]=1)[CH2:6][NH:7][C:8](=[O:28])[C:9]1[CH:14]=[CH:13][N:12]=[C:11]([C:15]2[CH:20]=[C:19]([N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)[CH:18]=[CH:17][C:16]=2[NH2:27])[CH:10]=1.ClC[C:36]1[N:41]=[C:40]([C:42]([OH:44])=O)[CH:39]=[CH:38][CH:37]=1.[CH3:45]CN=C=NCCCN(C)C.[ClH:56]>ClCCl.CN(C)C1C=CN=CC=1>[F:33][C:2]([F:1])([F:32])[C:3]1[CH:4]=[C:5]([CH:29]=[CH:30][CH:31]=1)[CH2:6][NH:7][C:8](=[O:28])[C:9]1[CH:14]=[CH:13][N:12]=[C:11]([C:15]2[CH:20]=[C:19]([N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)[CH:18]=[CH:17][C:16]=2[NH:27][C:42](=[O:44])[C:40]2([CH2:45][Cl:56])[CH:39]=[CH:38][CH:37]=[CH:36][NH:41]2)[CH:10]=1

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 186897392-Pyridinecarboxylic acid, 6-(chloromethyl)-HCID 66586742HCID 66586742, compound

Product 1

HCID 86705954N-(3-(trifluoromethyl)benzyl)-2-(2-(2-(chloromethyl)picolinamido)-5-(piperidin-1-yl)phenyl)isonicotinamideYield 82%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

Into a 50-mL 1-neck bottle, was placed a solution of N-(3-(trifluoromethyl)benzyl)-2-(2-amino-5-(piperidin-1-yl)phenyl)isonicotinamide (1.83 g, 4.03 mmol, 1.00 equiv) in dichloromethane (30 mL), 6-(chloromethyl)picolinic acid (1.04 g, 6.05 mmol, 1.50 equiv), EDC.HCl (1.54 g, 8.06 mmol, 2.00 equiv), and 4-dimethylaminopyridine (490 mg, 4.02 mmol, 1.00 equiv). The resulting solution was stirred for 4 h at 25° C. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column and eluted with dichloromethane:methanol (100:1). The product was obtained as 2 g (82%) of a yellow solid. 1H-NMR (300 MHz, DMSO-d6, ppm): δ 13.01 (s, 1H), 9.54 (t, J=8.7 Hz, 1H), 9.09 (d, J=5.1 Hz, 1H), 8.51 (d, J=9.0 Hz, 1H), 8.25 (s, 1H), 8.12-8.04 (m, 2H), 7.87-7.37 (m, 6H), 7.36 (s, 1H), 7.14 (dd, J=9.0 Hz, 1H), 4.95 (s, 2H), 4.65 (t, J=4.8 Hz, 2H), 3.34-3.20 (m, 4H), 1.67-1.55 (m, 6H). MS (ES, m/z): 608 [M+H]+.

Workup

  1. concentrationThe resulting mixture was concentrated under vacuum
  2. washeluted with dichloromethane:methanol (100:1)

Sources & evidence

ORD record
ord-fdff924d94504b4f9170d50959927d20
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

Loading…