Pyridine → N1-methyl-N1-(2-morpholinoethyl)-N3-(4-(piperidin-1-yl)-2-((1-(3-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-3-yl)carbamoyl)phenyl)isophthalamide

HRID 926843Notes

Reaction equation

HRID 926843 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[N: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].N1C=CC=CC=1.[CH3:38][N:39]([CH2:51][CH2:52][N:53]1[CH2:58][CH2:57][O:56][CH2:55][CH2:54]1)[C:40]([C:42]1[CH:43]=[C:44]([CH:48]=[CH:49][CH:50]=1)[C:45](Cl)=[O:46])=[O:41]>ClCCl>[CH3:38][N:39]([CH2:51][CH2:52][N:53]1[CH2:58][CH2:57][O:56][CH2:55][CH2:54]1)[C:40](=[O:41])[C:42]1[CH:50]=[CH:49][CH:48]=[C:44]([C:45]([NH:1][C:2]2[CH:25]=[CH:24][C:23]([N:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)=[CH:22][C:3]=2[C:4](=[O:5])[NH:6][C:7]2[N:11]=[CH:10][N:9]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:19])[F:20])[CH:13]=3)[N:8]=2)=[O:46])[CH:43]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 665877022-amino-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-3-yl)benzamideHCID 867052033-(Methyl(2-morpholinoethyl)carbamoyl)benzoyl chloride

Product 1

HCID 56646805N1-methyl-N1-(2-morpholinoethyl)-N3-(4-(piperidin-1-yl)-2-((1-(3-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-3-yl)carbamoyl)phenyl)isophthalamideYield 15%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
2.5 °C

Procedure

Into a 100-mL round bottom flask, was placed a solution of 2-amino-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-3-yl)benzamide (150 mg, 0.35 mmol, 1.00 equiv) in dichloromethane (20 mL), and pyridine (83 mg, 1.05 mmol, 3.01 equiv). This was followed by dropwise addition of a solution of 3-(methyl(2-morpholinoethyl)carbamoyl)benzoyl chloride (130 mg, 0.42 mmol, 1.20 equiv) in dichloromethane (10 mL) with stirring at 0-5° C. The resulting solution was stirred for 3 h at room temperature. The resulting solution was diluted with 30 mL of dichloromethane. The resulting mixture was washed with 1×20 mL of NH4Cl and 2×20 mL of brine, dried over anhydrous sodium sulfate, and 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 36.7 mg (15%) of a yellow solid. 1H-NMR (400 MHz, DMSO, ppm): δ 11.43-11.33(m, 2H), 9.70(s, 1H), 9.43(s, 1H), 8.77(s, 1H), 8.26-8.18 (m, 3H), 8.06-7.93 (m, 2H), 7.86-7.79(m, 2H), 7.68-7.62(m, 2H), 7.52(s, 1H), 7.30-7.28(d, J=6.9 Hz, 1H), 4.59-4.57(m, 1H), 4.18-3.83(m, 27H), 3.44(s, 3H), 3.27-3.26 (m, 5H), 3.18 (s, 3H), 2.96(s, 4H), 1.69(s, 4H), 1.59-1.52(m, 3H). MS (ES, m/z): 705 [M+H]+.

Workup

  1. customInto a 100-mL round bottom flask, was placed
  2. stirringThe resulting solution was stirred for 3 h at room temperature
  3. washThe resulting mixture was washed with 1×20 mL of NH4Cl and 2×20 mL of brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe crude product (200 mg) was purified by reverse phase HPLC
  7. washeluting with a water/CH3CN gradient
  8. additioncontaining 0.05% TFA

Sources & evidence

ORD record
ord-244e08405c1841eb8b01f7be99801ddc
Source dataset
uspto-grants-2016_03
Patent number
US09289430B2

Reaction notes

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