Potassium Carbonate → HCID 58180891, compound

HRID 1772845Notes

Reaction equation

HRID 1772845 reaction equation
[C:1]([CH:3]=[CH:4][CH2:5][N:6]1[CH2:11][CH2:10][N:9]([C:12]([C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][C:15]=2[F:22])=[O:13])[CH:8]([CH2:23][OH:24])[CH2:7]1)#[N:2].[NH:25]1[CH:29]=[C:28]([C:30]2[C:31]3[CH:38]=[CH:37][N:36](COCC[Si](C)(C)C)[C:32]=3[N:33]=[CH:34][N:35]=2)[CH:27]=[N:26]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:1]([CH2:3][CH:4]([N:25]1[CH:29]=[C:28]([C:30]2[C:31]3[CH:38]=[CH:37][NH:36][C:32]=3[N:33]=[CH:34][N:35]=2)[CH:27]=[N:26]1)[CH2:5][N:6]1[CH2:11][CH2:10][N:9]([C:12]([C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][C:15]=2[F:22])=[O:13])[CH:8]([CH2:23][OH:24])[CH2:7]1)#[N:2]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 426313464-(1H-Pyrazol-4-yl)-7-(2-(trimethylsilyl)ethoxy)methyl-7 H-pyrrolo(2,3-d)-pyrimidineHCID 67054967HCID 67054967, compound

Product 1

HCID 58180891HCID 58180891, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-{[4-[3-cyanoprop-2-en-1-yl]-2-(hydroxymethyl)piperazin-1-yl]carbonyl}-3-fluorobenzonitrile (46 mg, 0.14 mmol, as a mixture of E- and Z-mixtures from Step 2) was combined with 4-(1H-pyrazol-4-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (29 mg, 0.093 mmol, prepared as described in WO 2007/070514 Example 65) in DMF (0.14 mL) and potassium carbonate (0.0414 g, 0.299 mmol) was added. The reaction mixture was stirred overnight. The mixture was then filtered and the filtrate was diluted with EtOAc. This solution was washed with water (thrice), brine; dried over sodium sulfate, decanted and concentrated. The crude was then stirred in 1:1 DCM:TFA (4 mL) for 1 h and the solvent removed in vacuo. The residue was then stirred with 0.2 mL ethylenediamine in 1.5 mL MeOH for 30 min. Preparative HPLC-MS (C18, eluting with a gradient of H2O/MeCN containing 0.15% NH4OH) was used to purify product—a mixture of diastereomers (24 mg, 50%). 1H NMR (400 MHz, DMSO-d6, mixture of diastereomers and rotamers): δ 12.12 (br s, 2H), 8.81, 8.80, 8.78, 8.78 (4s, 2H), 8.68, 8.67 (2s, 2H), 8.37, 8.37, 8.36 (3s, 2H), 7.99-7.91 (m, 2H), 7.80-7.72 (m, 2H), 7.63-7.50 (m, 4H), 6.99-6.95 (m, 2H), 5.07-1.84 (m, 28H); LCMS (M+H)+: 514.2.

Workup

  1. additionwas added
  2. filtrationThe mixture was then filtered
  3. additionthe filtrate was diluted with EtOAc
  4. washThis solution was washed with water (thrice), brine
  5. dry with materialdried over sodium sulfate
  6. customdecanted
  7. concentrationconcentrated
  8. stirringThe crude was then stirred in 1:1 DCM
  9. waitTFA (4 mL) for 1 h
  10. customthe solvent removed in vacuo
  11. stirringThe residue was then stirred with 0.2 mL ethylenediamine in 1.5 mL MeOH for 30 min
  12. washPreparative HPLC-MS (C18, eluting with a gradient of H2O/MeCN containing 0.15% NH4OH)
  13. customto purify product—a
  14. additionmixture of diastereomers (24 mg, 50%)

Sources & evidence

ORD record
ord-849bb96c9d8c457f924446ca943300e5
Source dataset
uspto-grants-2016_02
Patent number
US09249145B2

Reaction notes

Loading…