Water → N1-(4-Chloro-2-((1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)carbamoyl)phenyl)-N3-methyl-N3-(2-morpholinoethyl)isophthalamide 2,2,2-trifluoroacetate

HRID 926887Notes

Reaction equation

HRID 926887 reaction equation
[NH2:1][C:2]1[CH:25]=[CH:24][C:23]([Cl:26])=[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].N1C=CC=CC=1.[CH3:33][N:34]([CH2:46][CH2:47][N:48]1[CH2:53][CH2:52][O:51][CH2:50][CH2:49]1)[C:35]([C:37]1[CH:38]=[C:39]([CH:43]=[CH:44][CH:45]=1)[C:40](Cl)=[O:41])=[O:36].[OH2:54]>ClCCl>[F:19][C:18]([F:21])([F:20])[C:14]([OH:36])=[O:54].[Cl:26][C:23]1[CH:24]=[CH:25][C:2]([NH:1][C:40](=[O:41])[C:39]2[CH:43]=[CH:44][CH:45]=[C:37]([C:35]([N:34]([CH3:33])[CH2:46][CH2:47][N:48]3[CH2:49][CH2:50][O:51][CH2:52][CH2:53]3)=[O:36])[CH:38]=2)=[C:3]([C:4](=[O:5])[NH:6][C:7]2[CH:11]=[CH:10][N:9]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:20])([F:21])[F:19])[CH:13]=3)[N:8]=2)[CH:22]=1

Participants

6

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 665876402-amino-5-chloro-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamideHCID 867052033-(Methyl(2-morpholinoethyl)carbamoyl)benzoyl chloride

Product 1

HCID 56644135N1-(4-Chloro-2-((1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)carbamoyl)phenyl)-N3-methyl-N3-(2-morpholinoethyl)isophthalamide 2,2,2-trifluoroacetateYield 22%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Into a 50-mL round bottom flask, was placed a solution of 2-amino-5-chloro-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamide 6d (150 mg, 0.39 mmol, 1.00 equiv) in dichloromethane (6 mL), and pyridine (93.6 mg, 1.18 mmol, 3.00 equiv). To this was added dropwise, a solution of 3-(methyl(2-morpholinoethyl)carbamoyl)benzoyl chloride 1f (147 mg, 0.47 mmol, 1.20 equiv) in dichloromethane (2 mL) over 10 min with stirring at 0° C. The resulting solution was stirred for 1 h at room temperature. The resulting solution was diluted with 2 mL of water, and adjusted to pH 8 with NH3H2O (2 mol/L). The resulting solution was extracted with 2×5 mL of dichloromethane and the organic layers combined, dried over sodium sulfate, and 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 67.2 mg (22%) of a white solid. 1H-NMR (300 MHz, DMSO, ppm): δ 11.67 (s, 1H), 11.54 (s, 1H), 9.62 (s, 1H), 8.68-8.67 (d, J=2.7 Hz, 1H), 8.71-8.38 (d, J=9.0 Hz, 1H), 8.16-8.02 (m, 5H), 7.79-7.65 (m, 5H), 6.968-6.960 (d, J=2.4 Hz, 1H), 4.01(s, 2H), 3.84 (s, 2H), 3.42 (s, 6H), 3.18 (s, 2H), 2.98(s, 3H). MS (ES, m/z): 655 [M+H]+.

Workup

  1. customInto a 50-mL round bottom flask, was placed
  2. additionTo this was added dropwise
  3. extractionThe resulting solution was extracted with 2×5 mL of dichloromethane
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated 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-5572575f3bad446db1edca732e0bce76
Source dataset
uspto-grants-2016_03
Patent number
US09289430B2

Reaction notes

Loading…