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

HRID 2406098Notes

Reaction equation

HRID 2406098 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:55]=[CH:54][C:53]([N:56]2[CH2:61][CH2:60][CH2:59][CH2:58][CH2:57]2)=[CH:52][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]=[CH:48][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:55]=[CH:54][C:53]([N:56]3[CH2:57][CH2:58][CH2:59][CH2:60][CH2:61]3)=[CH:52][C:36]=2[C:37](=[O:38])[NH:39][C:40]2[CH:45]=[N:44][C:43]([C:46]3[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=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 665870272-amino-N-(2-phenylpyrimidin-5-yl)-5-(piperidin-1-yl)benzamide

Product 1

HCID 56602208N1-Methyl-N1-(2-morpholinoethyl)-N3-(2-((2-phenylpyrimidin-5-yl)carbamoyl)-4-(piperidin-1-yl)phenyl)isophthalamideYield 32.6%

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 (314 mg, 1.08 mmol, 2.00 equiv) in dichloromethane (10 mL), EDC.HCl (155 mg, 0.81 mmol, 1.50 equiv), 4-dimethylaminopyridine (99 mg, 0.81 mmol, 1.50 equiv), and 2-amino-N-(2-phenylpyrimidin-5-yl)-5-(piperidin-1-yl)benzamide (200 mg, 0.54 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 114 mg (28%) of a yellow solid. 1H-NMR (300 MHz, DMSO, ppm): δ 10.98 (m, 2H), 9.70 (s, 1H), 9.29 (s, 2H), 8.35 (m, 2H), 8.01 (m, 3H), 7.63 (m, 2H), 7.52 (m, 4H), 7.28 (m, 1H), 4.03 (m, 2H), 3.82 (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): 648 [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-52a504709d454ce6a0331ef79a2276b8
Source dataset
uspto-grants-2014_08
Patent number
US08809339B2

Reaction notes

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