1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 2-(3-(((2-(diethylamino)ethyl)(methyl)amino)methyl)benzamido)-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamide

HRID 2409864Notes

Reaction equation

HRID 2409864 reaction equation
[NH2:1][C:2]1[CH:25]=[CH:24][C:23]([N:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)=[CH:22][C:3]=1[C:4]([NH:6][C:7]1[CH:11]=[CH:10][N:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[N:8]=1)=[O:5].[CH2:32]([N:34]([CH2:49][CH3:50])[CH2:35][CH2:36][N:37]([CH2:39][C:40]1[CH:41]=[C:42]([CH:46]=[CH:47][CH:48]=1)[C:43](O)=[O:44])[CH3:38])[CH3:33].CCN=C=NCCCN(C)C.Cl>ClCCl.CN(C)C1C=CN=CC=1>[CH2:49]([N:34]([CH2:32][CH3:33])[CH2:35][CH2:36][N:37]([CH2:39][C:40]1[CH:41]=[C:42]([CH:46]=[CH:47][CH:48]=1)[C:43]([NH:1][C:2]1[CH:25]=[CH:24][C:23]([N:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)=[CH:22][C:3]=1[C:4]([NH:6][C:7]1[CH:11]=[CH:10][N:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:20])([F:21])[F:19])[CH:13]=2)[N:8]=1)=[O:5])=[O:44])[CH3:38])[CH3:50]

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665868393-(((2-(Diethylamino)ethyl)(methyl)amino)methyl)benzoic acidHCID 665874172-amino-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamide

Product 1

HCID 566439302-(3-(((2-(diethylamino)ethyl)(methyl)amino)methyl)benzamido)-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamideYield 37.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
30 °C

Procedure

Into a 50-mL round bottom flask, was placed a solution of 2-amino-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamide 8d (100 mg, 0.23 mmol, 1.00 equiv) in dichloromethane (5 mL), 3-(((2-(diethylamino)ethyl)(methyl)amino)methyl)benzoic acid (74 mg, 0.28 mmol, 1.20 equiv), EDC.HCl (90 mg, 0.47 mmol, 2.01 equiv), and 4-dimethylaminopyridine (43 mg, 0.35 mmol, 1.51 equiv). The resulting solution was stirred overnight at 30° C. in an oil bath. The reaction progress was monitored by LCMS. The resulting mixture was washed with 3×10 mL of water and 1×10 mL of brine. The mixture was dried over sodium sulfate. The solids were filtered out. The resulting mixture was concentrated under vacuum. The crude product (150 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 58.5 mg (32%) of a yellow solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 8.502-8.532 (d, J=9.0 Hz, 1H), 8.277-8.286 (m, 1H), 8.060 (s, 1H), 7.851-7.966 (m, 4H), 7.475-7.610 (m, 5H), 6.949-6.958 (m, 1H), 3.922 (s, 2H), 3.450-3.485 (m, 4H), 3.273-3.316 (m, 2H), 3.035-3.108 (m, 4H), 2.957-2.998 (m, 2H), 2.449-2.475 (m, 3H), 1.857-1.872 (m, 4H), 1.666-1.683 (m, 2H), 1.139-1.200 (m, 6H). MS (ES, m/z): 676 [M+H]+.

Workup

  1. customInto a 50-mL round bottom flask, was placed
  2. washThe resulting mixture was washed with 3×10 mL of water and 1×10 mL of brine
  3. dry with materialThe mixture was dried over sodium sulfate
  4. filtrationThe solids were filtered out
  5. concentrationThe resulting mixture was concentrated under vacuum
  6. customThe crude product (150 mg) was purified by reverse phase HPLC
  7. washeluting with a water/CH3CN gradient
  8. additioncontaining 0.05% TFA

Sources & evidence

ORD record
ord-79a496db15624eaaabe33e0d103a0bc7
Source dataset
uspto-grants-2014_08
Patent number
US08815910B2

Reaction notes

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