Potassium Iodide → 2-(2-(3-(((3-((2-methoxyethyl)amino)-3-oxopropyl)(methyl)amino)-methyl)benzamido)-5-(piperidin-1-yl)phenyl)-N-(3-(trifluoromethyl)benzyl)-isonicotinamide

HRID 625360Notes

Reaction equation

HRID 625360 reaction equation
[F:1][C:2]([F:43])([F:42])[C:3]1[CH:4]=[C:5]([CH:39]=[CH:40][CH:41]=1)[CH2:6][NH:7][C:8](=[O:38])[C:9]1[CH:14]=[CH:13][N:12]=[C:11]([C:15]2[CH:20]=[C:19]([N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)[CH:18]=[CH:17][C:16]=2[NH:27][C:28](=[O:37])[C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([CH2:35]Br)[CH:30]=2)[CH:10]=1.[CH3:44][O:45][CH2:46][CH2:47][NH:48][C:49](=[O:54])[CH2:50][CH2:51][NH:52][CH3:53].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C)C=O.C(OCC)(=O)C>[CH3:44][O:45][CH2:46][CH2:47][NH:48][C:49](=[O:54])[CH2:50][CH2:51][N:52]([CH2:35][C:31]1[CH:30]=[C:29]([CH:34]=[CH:33][CH:32]=1)[C:28]([NH:27][C:16]1[CH:17]=[CH:18][C:19]([N:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)=[CH:20][C:15]=1[C:11]1[CH:10]=[C:9]([CH:14]=[CH:13][N:12]=1)[C:8]([NH:7][CH2:6][C:5]1[CH:39]=[CH:40][CH:41]=[C:3]([C:2]([F:43])([F:42])[F:1])[CH:4]=1)=[O:38])=[O:37])[CH3:53]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 43827811N-(2-methoxyethyl)-3-(methylamino)propanamideHCID 665867752-(2-(3-(bromomethyl)benzamido)-5-(piperidin-1-yl)phenyl)-N-(3-(trifluoromethyl)benzyl)isonicotinamide

Product 1

HCID 680873772-(2-(3-(((3-((2-methoxyethyl)amino)-3-oxopropyl)(methyl)amino)-methyl)benzamido)-5-(piperidin-1-yl)phenyl)-N-(3-(trifluoromethyl)benzyl)-isonicotinamideYield 28.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

Into a 8-mL round-bottom flask, was placed a solution of N-(3-(trifluoromethyl)benzyl)-2-(2-(3-(bromomethyl)benzamido)-5-(piperidin-1-yl)phenyl)-isonicotinamide 42a (250 mg, 0.31 mmol, 1.00 equiv, 80%) in N,N-dimethylformamide (6 mL), N-(2-methoxyethyl)-3-(methylamino)propanamide (185 mg, 1.04 mmol, 3.00 equiv, 90%), potassium carbonate (106 mg, 0.77 mmol, 2.00 equiv), and potassium iodide (32 mg, 0.19 mmol, 0.50 equiv). The resulting solution was stirred for 5 h at 60° C. The resulting solution was diluted with 100 mL of ethyl acetate. The resulting mixture was washed with 1×20 mL of 10% sodium bicarbonate. The resulting mixture was washed with 1×20 mL of brine, dried over sodium sulfate, and concentrated under vacuum. The crude product was purified by Flash-Prep-HPLC with water:methanol (0.05% TFA) (10:90). The product was obtained as 63.7 mg (23%) of a yellow solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 8.87 (d, J=6 Hz, 1H), 8.29 (m, 2H), 8.06 (m, 2H), 7.70 (m, 8H), 7.31 (d, J=9 Hz, 1H), 4.70 (s, 2H), 4.50 (m, 2H), 3.43 (m, 2H), 3.39 (m, 6H), 2.89 (s, 3H), 2.76 (m, 2H), 1.86 (m, 4H), 1.73 (m, 2H). MS (ES, m/z): 731 [M+H]+.

Workup

  1. customInto a 8-mL round-bottom flask, was placed
  2. washThe resulting mixture was washed with 1×20 mL of 10% sodium bicarbonate
  3. washThe resulting mixture was washed with 1×20 mL of brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe crude product was purified by Flash-Prep-HPLC with water

Sources & evidence

ORD record
ord-fad1c3119a5b442dab26c3ad15831ff4
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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