Potassium Carbonate → HCID 71279632, compound

HRID 246538Notes

Reaction equation

HRID 246538 reaction equation
Cl[CH2:2][C:3]([NH:5][CH3:6])=[O:4].C(=O)([O-])[O-].[K+].[K+].[C:13]([NH:17][C:18]([C:20]1[C:28]2[C:23](=[N:24][CH:25]=[C:26]([C:29]3[C:37]4[C:32](=[CH:33][CH:34]=[C:35]([O:38][CH:39]([F:41])[F:40])[CH:36]=4)[NH:31][N:30]=3)[N:27]=2)[N:22]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[CH:21]=1)=[O:19])([CH3:16])([CH3:15])[CH3:14]>CN(C=O)C>[C:13]([NH:17][C:18]([C:20]1[C:28]2[C:23](=[N:24][CH:25]=[C:26]([C:29]3[C:37]4[C:32](=[CH:33][CH:34]=[C:35]([O:38][CH:39]([F:40])[F:41])[CH:36]=4)[N:31]([CH2:2][C:3]([NH:5][CH3:6])=[O:4])[N:30]=3)[N:27]=2)[N:22]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[CH:21]=1)=[O:19])([CH3:16])([CH3:15])[CH3:14]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 667732-chloro-N-methylacetamideHCID 712795662-(5-difluoromethoxy-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

Product 1

HCID 71279632HCID 71279632, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
70 °C

Procedure

To a stirred solution of 2-chloro-N-methylacetamide (80 mg, 744 μmol) in DMF (28.0 mL) under Ar, potassium carbonate (280 mg, 2.03 mmol) was added at 25° C. After 1 h, N-tert-butyl-2-(5-(difluoromethoxy)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (70 mg, 132 μmol) in DMF (7.00 mL) was added and the reaction was stirred at 70° C. After 6 h, the reaction was cooled to 25° C. and quenched with water (350 mL). The product was extracted with ethyl acetate (2×250 mL). The organic layer was dried over sodium sulfate, filtered through Celite, and the solvent removed in vacuo to give a beige solid. The solid was triturated in hexanes (20 mL), filtered and dried in vacuo (200 mTorr, 25° C.) to give N-tert-butyl-2-(5-(difluoromethoxy)-1-(2-(methylamino)-2-oxoethyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (62.2 mg, 103 μmol, 78%) as a light brown solid. MS (M)'=602; 1H NMR (DMSO-d6) δ: 9.10 (s, 1H), 8.60 (s, 1H), 8.22 (m, 2H), 7.88 (s, 1H), 7.82 (d, J=9.0 Hz, 1H), 7.41 (dd, J=2.3, 9.0 Hz, 1H), 7.21 (t, J=74.5 Hz, 1H), 5.73 (s, 2H), 5.27 (s 2H), 3.58 (t, J=8.0 Hz, 2H), 2.65 (d, J=4.5 Hz, 3H), 1.51 (s, 9H), 0.86 (t, J=7.8 Hz, 2H), −0.08 (s, 9H).

Workup

  1. waitAfter 6 h
  2. temperaturethe reaction was cooled to 25° C.
  3. customquenched with water (350 mL)
  4. extractionThe product was extracted with ethyl acetate (2×250 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered through Celite
  7. customthe solvent removed in vacuo
  8. customto give a beige solid
  9. customThe solid was triturated in hexanes (20 mL)
  10. filtrationfiltered
  11. customdried in vacuo (200 mTorr, 25° C.)

Sources & evidence

ORD record
ord-b58377273997408f9716467f16fcd6ed
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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