Potassium Iodide → HCID 66586764, compound

HRID 1408111Notes

Reaction equation

HRID 1408111 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.[N:44]1([C:50](=[O:52])[CH3:51])[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C)C=O>[C:50]([N:44]1[CH2:49][CH2:48][N:47]([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)[CH2:46][CH2:45]1)(=[O:52])[CH3:51]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 837951-AcetylpiperazineHCID 66586774HCID 66586774, compound

Product 1

HCID 66586764HCID 66586764, compoundYield 63.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

Into a 8-mL sealed tube, was placed a solution of 6-(chloromethyl)-N-(4-(piperidin-1-yl)-2-(4-(3-(trifluoromethyl)benzylcarbamoyl)pyridin-2-yl)phenyl)picolinamide (120 mg, 0.20 mmol, 1.00 equiv) in N,N-dimethylformamide (5 mL), 1-(piperazin-1-yl)ethanone (37.9 mg, 0.30 mmol, 1.50 equiv), potassium carbonate (82 mg, 0.59 mmol, 3.00 equiv), and potassium iodide (7 mg, 0.04 mmol, 0.20 equiv). The resulting solution was stirred for 3 h at 65° C. The reaction was then quenched with 10 mL of water. The resulting solution was extracted with 3×30 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3×30 mL of brine, dried over sodium sulfate, and concentrated under vacuum. The crude product (100 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 89.2 mg (56%) of a yellow solid. 1H-NMR (300 MHz, DMSO-d6, ppm): δ 12.56 (s, 1H), 9.54 (t, J=6.0 Hz, 1H), 9.08 (d, J=5.1 Hz, 1H), 8.38 (d, J=8.7 Hz, 1H), 8.25-8.17 (m, 3H), 7.84 (d, J=3.9 Hz, 2H), 7.71-7.58 (m, 5H), 7.51 (s, 1H), 4.63 (d, J=5.7 Hz, 2H), 4.49 (s, 2H), 3.31-3.21 (m, 10H), 2.01 (s, 3H), 1.72-1.59 (m, 6H). MS (ES, m/z): 700 [M+H]+.

Workup

  1. customInto a 8-mL sealed tube
  2. customThe reaction was then quenched with 10 mL of water
  3. extractionThe resulting solution was extracted with 3×30 mL of ethyl acetate
  4. washThe resulting mixture was washed with 3×30 mL of brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe crude product (100 mg) was purified by reverse phase HPLC
  8. washeluting with a water/CH3CN gradient
  9. additioncontaining 0.05% TFA

Sources & evidence

ORD record
ord-ccbfe42aa4c845718054ed1f243a5429
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

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