Cesium acetate → HCID 178485471, compound

HRID 707307Notes

Reaction equation

HRID 707307 reaction equation
C(O[C:6](=O)[NH:7][C@H:8]1[CH2:11][C@H:10]([N:12]2[C:16]3=[N:17][CH:18]=[CH:19][CH:20]=[C:15]3[C:14]([CH3:22])([CH3:21])[C:13]2=[O:23])[CH2:9]1)(C)(C)C.C([O-])(=O)C.[Cs+].BrC1[CH:40]=[CH:39][C:34]([C:35]([NH:37][CH3:38])=[O:36])=[CH:33][N:32]=1>[Cu]>[CH3:22][C:14]1([CH3:21])[C:15]2[C:16](=[N:17][CH:18]=[CH:19][CH:20]=2)[N:12]([C@H:10]2[CH2:11][C@H:8]([NH:7][C:6]3[CH:40]=[CH:39][C:34]([C:35]([NH:37][CH3:38])=[O:36])=[CH:33][N:32]=3)[CH2:9]2)[C:13]1=[O:23]

Participants

5

Reactant 3

HCID 5152919Cesium acetateHCID 230921426-Bromo-N-methylnicotinamideHCID 178454100HCID 178454100, compound

Product 1

HCID 178485471HCID 178485471, compoundYield 36.7%

Reagents, catalysts & solvents 1

HCID 23978CopperCatalyst

Conditions

Temperature
100 °C

Procedure

Intermediate 26 (100 mg, 0.373 mmol), cesium acetate (516 mg, 2.69 mmol), 6-bromo-n-methylnicotinamide (120 mg, 0.560 mmol), and copper (1.899 mg, 0.030 mmol) were weighed into a microwave vial. The vial was evacuated and flushed with nitrogen. DMSO (467 μl) was then added and the mixture was heated at 100° C. for 20 h. The mixture was diluted with ethyl acetate and washed with aqueous ammonium hydroxide. The aqueous layer was back extracted with ethyl acetate and the combined organics dried with magnesium sulfate and evaporated to dryness under reduced pressure. The crude product was purified by silica chromatography, eluting with a gradient of hexane/ethyl acetate (50-100%) to provide 6-((trans-3-(3,3-dimethyl-2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-1-yl)cyclobutyl)amino)-N-methylnicotinamide (50 mg, 0.137 mmol, 36.6% yield) as off-white solid. M+1: 366. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.38 (s, 6 H) 2.28-2.40 (m, 2 H) 3.00 (d, J=4.82 Hz, 3 H) 3.39-3.54 (m, 2 H) 4.50 (br. s., 1 H) 5.28 (quin, J=8.59 Hz, 1 H) 5.38 (br. d, J=4.80 Hz, 1 H) 5.98 (br. s., 1 H) 6.34 (d, J=8.77 Hz, 1 H) 6.96 (dd, J=7.31, 5.26 Hz, 1 H) 7.43 (dd, J=7.16, 1.61 Hz, 1 H) 7.91 (dd, J=8.70, 2.41 Hz, 1 H) 8.18 (dd, J=5.26, 1.61 Hz, 1 H) 8.51 (d, J=2.05 Hz, 1 H)

Workup

  1. customThe vial was evacuated
  2. customflushed with nitrogen
  3. additionDMSO (467 μl) was then added
  4. additionThe mixture was diluted with ethyl acetate
  5. washwashed with aqueous ammonium hydroxide
  6. extractionThe aqueous layer was back extracted with ethyl acetate
  7. dry with materialthe combined organics dried with magnesium sulfate
  8. customevaporated to dryness under reduced pressure
  9. customThe crude product was purified by silica chromatography
  10. washeluting with a gradient of hexane/ethyl acetate (50-100%)

Sources & evidence

ORD record
ord-9061781579084011ba3d970192ff2b49
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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