Potassium Carbonate → HCID 50995826, compound

HRID 1772847Notes

Reaction equation

HRID 1772847 reaction equation
C(=O)([O-])[O-].[K+].[K+].[C:7]([CH:9]=[CH:10][CH2:11][N:12]1[CH2:17][CH2:16][N:15]([C:18]([C:20]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][C:21]=2[F:28])=[O:19])[C@H:14]([CH3:29])[CH2:13]1)#[N:8].[NH:30]1[CH:34]=[C:33]([C:35]2[C:36]3[CH:43]=[CH:42][N:41](COCC[Si](C)(C)C)[C:37]=3[N:38]=[CH:39][N:40]=2)[CH:32]=[N:31]1>CN(C=O)C>[C:7]([CH2:9][CH:10]([N:30]1[CH:34]=[C:33]([C:35]2[C:36]3[CH:43]=[CH:42][NH:41][C:37]=3[N:38]=[CH:39][N:40]=2)[CH:32]=[N:31]1)[CH2:11][N:12]1[CH2:17][CH2:16][N:15]([C:18]([C:20]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][C:21]=2[F:28])=[O:19])[C@H:14]([CH3:29])[CH2:13]1)#[N:8]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 426313464-(1H-Pyrazol-4-yl)-7-(2-(trimethylsilyl)ethoxy)methyl-7 H-pyrrolo(2,3-d)-pyrimidineHCID 67054940HCID 67054940, compound

Product 1

HCID 50995826HCID 50995826, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Potassium carbonate (0.170 g, 1.23 mmol) was added to a mixture of 4-({(2R)-4-[3-cyanoprop-2-en-1-yl]-2-methylpiperazin-1-yl}carbonyl)-3-fluorobenzonitrile (0.12 g, 0.38 mmol, mixture of E- and Z-isomers from Step 2) and 4-(1H-pyrazol-4-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (0.12 g, 0.38 mmol, prepared as described in WO 2007/070514 Example 65) in DMF (0.59 mL) and the mixture was stirred overnight. The reaction mixture was then filtered and the filtrate was diluted with EtOAc. The filtrate was then washed with water (thrice), followed by brine, dried over sodium sulfate, decanted and concentrated. A portion of the crude product was dissolved in a 1:1 mixture of DCM:TFA, stirred at RT for 1 h, and concentrated. The residue was dissolved in methanol (1 mL) and 0.2 mL of aqueous ammonium hydroxide was added. After stirring for 2 h, the reaction mixture was concentrated. Preparative HPLC-MS (C18, eluting with a gradient of H2O/MeCN containing 0.15% NH4OH) afforded product as a mixture of two diastereomers. 1H NMR (300 MHz, DMSO-d6, diastereomers, rotamers): δ 12.11 (br s, 2H), 8.84-8.79 (m, 2H), 8.68-8.66 (m, 2H), 8.37-8.35 (m, 2H), 8.02-7.93 (m, 2H), 7.80-7.73 (m, 2H), 7.64-7.53 (m, 4H), 6.99-6.94 (m, 2H), 5.07-4.85 (m, 2H), 4.71-4.51 (m, 1H), 4.34 (t, 1H), 3.58-1.94 (m, 20H), 1.19 (d, 1.5H), 1.12 (d, 1.5H), 1.05 (d, 1.5H), 0.94 (d, 1.5H); 19F NMR (300 MHz, DMSO-D6): −114.54 to −115.75 (m, 2F); LCMS (M+H)+: 498.2.

Workup

  1. filtrationThe reaction mixture was then filtered
  2. additionthe filtrate was diluted with EtOAc
  3. washThe filtrate was then washed with water (thrice)
  4. dry with materialdried over sodium sulfate
  5. customdecanted
  6. concentrationconcentrated
  7. dissolutionA portion of the crude product was dissolved in a 1:1 mixture of DCM
  8. stirringTFA, stirred at RT for 1 h
  9. concentrationconcentrated
  10. dissolutionThe residue was dissolved in methanol (1 mL)
  11. addition0.2 mL of aqueous ammonium hydroxide was added
  12. stirringAfter stirring for 2 h
  13. concentrationthe reaction mixture was concentrated
  14. washPreparative HPLC-MS (C18, eluting with a gradient of H2O/MeCN containing 0.15% NH4OH)
  15. customafforded product
  16. additionas a mixture of two diastereomers

Sources & evidence

ORD record
ord-512642d836e54b4c871abbd3da8719a0
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

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