Potassium Iodide → HCID 69631072, compound

HRID 625367Notes

Reaction equation

HRID 625367 reaction equation
Cl[CH2:2][C:3]1[N:8]=[C:7]([C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)=[CH:14][C:13]=2[C:24]2[CH:29]=[C:28]([C:30](=[O:43])[NH:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([F:42])([F:41])[F:40])[CH:34]=3)[CH:27]=[CH:26][N:25]=2)=[O:10])[CH:6]=[CH:5][CH:4]=1.[NH:44]1[CH2:49][CH2:48][CH:47]([NH:50][C:51](=[O:53])[CH3:52])[CH2:46][CH2:45]1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C)C=O>[C:51]([NH:50][CH:47]1[CH2:48][CH2:49][N:44]([CH2:2][C:3]2[N:8]=[C:7]([C:9]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([N:18]4[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]4)=[CH:14][C:13]=3[C:24]3[CH:29]=[C:28]([C:30](=[O:43])[NH:31][CH2:32][C:33]4[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([F:42])([F:41])[F:40])[CH:34]=4)[CH:27]=[CH:26][N:25]=3)=[O:10])[CH:6]=[CH:5][CH:4]=2)[CH2:45][CH2:46]1)(=[O:53])[CH3:52]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 14451564-AcetamidopiperidineHCID 66586774HCID 66586774, compound

Product 1

HCID 69631072HCID 69631072, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

Into a 50-mL round-bottom flask, was placed a solution of 6-(chloromethyl)-N-(4-(piperidin-1-yl)-2-(4-(3-(trifluoromethyl)benzylcarbamoyl)pyridin-2-yl)phenyl)picolinamide (100 mg, 0.16 mmol, 1.00 equiv) in N,N-dimethylformamide (2 mL), N-(piperidin-4-yl)acetamide (35 mg, 0.25 mmol, 1.50 equiv), potassium carbonate (70 mg, 0.51 mmol, 3.00 equiv), and potassium iodide (6 mg, 0.04 mmol, 0.20 equiv). The resulting solution was stirred overnight at 60° C. The reaction progress was monitored by LCMS. The solids were filtered out. The 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 70.8 mg (51%) of a yellow solid. 1H-NMR (300 MHz, DMSO-d6, ppm): δ 12.49 (s, 1H), 9.86 (m, 1H), 9.54 (m, 1H), 9.06 (m, 1H), 8.37-8.19 (d, J=9 Hz, 1H), 8.24-8.19 (m, 3H), 7.97-7.95 (d, J=6 Hz, 1H), 7.86-7.83 (m, 2H), 7.70-7.49 (m, 5H), 7.26 (m, 1H), 4.64-4.51 (m, 4H), 3.82 (m, 1H), 3.54-3.24 (m, 8H), 1.95-1.58 (m, 13H). MS (ES, m/z): 714 [M+H]+.

Workup

  1. customInto a 50-mL round-bottom flask, was placed
  2. filtrationThe solids were filtered out
  3. concentrationThe mixture was concentrated under vacuum
  4. customThe crude product (200 mg) was purified by reverse phase HPLC
  5. washeluting with a water/CH3CN gradient
  6. additioncontaining 0.05% TFA

Sources & evidence

ORD record
ord-3b646e9d7e114bd49afc3b9fcce58429
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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