1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 2-(3-(((2-(diethylamino)ethyl)(methyl)amino)methyl)benzamido)-N-(5-(3,4-dimethylphenyl)pyrimidin-2-yl)-5-(piperidin-1-yl)benzamide

HRID 2406091Notes

Reaction equation

HRID 2406091 reaction equation
[CH2:1]([N:3]([CH2:18][CH3:19])[CH2:4][CH2:5][N:6]([CH2:8][C:9]1[CH:10]=[C:11]([CH:15]=[CH:16][CH:17]=1)[C:12]([OH:14])=O)[CH3:7])[CH3:2].CCN=C=NCCCN(C)C.Cl.[NH2:32][C:33]1[CH:55]=[CH:54][C:53]([N:56]2[CH2:61][CH2:60][CH2:59][CH2:58][CH2:57]2)=[CH:52][C:34]=1[C:35]([NH:37][C:38]1[N:43]=[CH:42][C:41]([C:44]2[CH:49]=[CH:48][C:47]([CH3:50])=[C:46]([CH3:51])[CH:45]=2)=[CH:40][N:39]=1)=[O:36]>ClCCl.CN(C)C1C=CN=CC=1>[CH2:18]([N:3]([CH2:1][CH3:2])[CH2:4][CH2:5][N:6]([CH2:8][C:9]1[CH:10]=[C:11]([CH:15]=[CH:16][CH:17]=1)[C:12]([NH:32][C:33]1[CH:55]=[CH:54][C:53]([N:56]2[CH2:61][CH2:60][CH2:59][CH2:58][CH2:57]2)=[CH:52][C:34]=1[C:35]([NH:37][C:38]1[N:43]=[CH:42][C:41]([C:44]2[CH:49]=[CH:48][C:47]([CH3:50])=[C:46]([CH3:51])[CH:45]=2)=[CH:40][N:39]=1)=[O:36])=[O:14])[CH3:7])[CH3:19]

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665868393-(((2-(Diethylamino)ethyl)(methyl)amino)methyl)benzoic acidHCID 665869432-amino-N-(5-(3,4-dimethylphenyl)pyrimidin-2-yl)-5-(piperidin-1-yl)benzamide

Product 1

HCID 566019942-(3-(((2-(diethylamino)ethyl)(methyl)amino)methyl)benzamido)-N-(5-(3,4-dimethylphenyl)pyrimidin-2-yl)-5-(piperidin-1-yl)benzamideYield 74.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

Into a 10-mL round bottom flask, was placed a solution of 3-(((2-(diethylamino)ethyl)(methyl)amino)methyl)benzoic acid (118.8 mg, 0.45 mmol, 1.50 equiv) in dichloromethane (24 mL), EDC.HCl (171.6 mg, 0.90 mmol, 3.00 equiv), 4-dimethylaminopyridine (182.4 mg, 1.49 mmol, 5.00 equiv), and 2-amino-N-(5-(3,4-dimethylphenyl)pyrimidin-2-yl)-5-(piperidin-1-yl)benzamide (120 mg, 0.29 mmol, 1.00 equiv). The resulting solution was stirred for 8 h at 25° C. in an oil bath. The resulting mixture was concentrated under vacuum. The crude product (200 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 139.2 mg (62%) of a yellow solid. 1H-NMR (300 MHz, DMSO, ppm): δ 11.37 (s, 1H), 11.30 (s, 1H), 8.75 (d, J=6 Hz, 2H), 8.22 (d, J=9 Hz, 1H), 8.054 (s, 1H), 7.93 (d, J=6.3 Hz, 1H), 7.68˜7.60 (m, 2H), 7.53 (s, 1H), 7.31˜7.20 (m, 3H), 7.15 (d, J=7.2 Hz, 1H), 3.40˜3.12 (m, 13H), 2.59 (s, 2H), 2.32˜2.27 (m, 4H), 2.16 (s, 3H), 1.68 (m, 4H), 1.58˜1.57 (m, 2H), 1.21˜1.16 (m, 6H). MS (ES, m/z): 648 [M−H]+.

Workup

  1. customInto a 10-mL round bottom flask, was placed
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. customThe crude product (200 mg) was purified by reverse phase HPLC
  4. washeluting with a water/CH3CN gradient
  5. additioncontaining 0.05% TFA

Sources & evidence

ORD record
ord-803c5272617f4d66a3ee0728818029ce
Source dataset
uspto-grants-2014_08
Patent number
US08809339B2

Reaction notes

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