1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → N1-methyl-NI-(2-morpholinoethyl)-N3-(4-(piperidin-1-yl)-2-((2-(3-(trifluoromethyl)phenyl)pyrimidin-5-yl)carbamoyl)phenyl)isophthalamide

HRID 926788Notes

Reaction equation

HRID 926788 reaction equation
[CH3:1][N:2]([CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1)[C:3]([C:5]1[CH:6]=[C:7]([CH:11]=[CH:12][CH:13]=1)[C:8]([OH:10])=O)=[O:4].CCN=C=NCCCN(C)C.Cl.[NH2:34][C:35]1[CH:59]=[CH:58][C:57]([N:60]2[CH2:65][CH2:64][CH2:63][CH2:62][CH2:61]2)=[CH:56][C:36]=1[C:37]([NH:39][C:40]1[CH:41]=[N:42][C:43]([C:46]2[CH:51]=[CH:50][CH:49]=[C:48]([C:52]([F:55])([F:54])[F:53])[CH:47]=2)=[N:44][CH:45]=1)=[O:38]>ClCCl.CN(C)C1C=CN=CC=1>[CH3:1][N:2]([CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1)[C:3](=[O:4])[C:5]1[CH:13]=[CH:12][CH:11]=[C:7]([C:8]([NH:34][C:35]2[CH:59]=[CH:58][C:57]([N:60]3[CH2:65][CH2:64][CH2:63][CH2:62][CH2:61]3)=[CH:56][C:36]=2[C:37](=[O:38])[NH:39][C:40]2[CH:45]=[N:44][C:43]([C:46]3[CH:51]=[CH:50][CH:49]=[C:48]([C:52]([F:55])([F:54])[F:53])[CH:47]=3)=[N:42][CH:41]=2)=[O:10])[CH:6]=1

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665869413-(Methyl(2-morpholinoethyl)carbamoyl)benzoic acidHCID 665877992-amino-5-(piperidin-1-yl)-N-(2-(3-(trifluoromethyl)phenyl)pyrimidin-5-yl)benzamide

Product 1

HCID 56602207N1-methyl-NI-(2-morpholinoethyl)-N3-(4-(piperidin-1-yl)-2-((2-(3-(trifluoromethyl)phenyl)pyrimidin-5-yl)carbamoyl)phenyl)isophthalamideYield 83.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

Into a 50-mL round bottom flask, was placed a solution of 3-(methyl(2-morpholinoethyl)carbamoyl)benzoic acid (186 mg, 0.64 mmol, 2.00 equiv) in dichloromethane (10 mL), EDC.HCl (92 mg, 0.48 mmol, 1.50 equiv), 4-dimethylaminopyridine (59 mg, 0.48 mmol, 1.50 equiv), and 2-amino-5-(piperidin-1-yl)-N-(2-(3-(trifluoromethyl)phenyl)pyrimidin-5-yl)benzamide (140 mg, 0.32 mmol, 1.00 equiv). The resulting solution was stirred for 4 h at 25° C. 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 191 mg (71%) of a yellow solid. 1H-NMR (300 MHz, DMSO, ppm): δ 10.97 (m, 2H), 9.66 (s, 1H), 9.25 (s, 2H), 8.63 (m, 2H), 7.99 (m, 4H), 7.79 (m, 1H), 7.63 (m, 2H), 7.42 (s, 1H), 7.26 (m, 1H), 3.99 (m, 2H), 3.83 (m, 2H), 3.61 (m, 4H), 3.43 (m, 2H), 3.24 (m, 6H), 2.95 (s, 3H), 1.59 (m, 6H). MS (ES, m/z): 716 [M+H]+.

Workup

  1. customInto a 50-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-2c827b2ea40240cf960fab4a579c6928
Source dataset
uspto-grants-2016_03
Patent number
US09289429B2

Reaction notes

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