Ethylenediamine → HCID 89630008, compound

HRID 882162Notes

Reaction equation

HRID 882162 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[C:15]2[C:14]([C:16]3[CH:17]=[C:18]([NH:22][C:23](=[O:27])[C:24]([CH3:26])=[CH2:25])[CH:19]=[CH:20][CH:21]=3)=[N:13][CH:12]=[N:11][C:10]=2[N:9](COCC[Si](C)(C)C)[CH:8]=1.C(C(O)=O)(F)(F)F.C(N)CN.[OH-].[Na+]>ClCCl>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[C:15]2[C:14]([C:16]3[CH:17]=[C:18]([NH:22][C:23](=[O:27])[C:24]([CH3:26])=[CH2:25])[CH:19]=[CH:20][CH:21]=3)=[N:13][CH:12]=[N:11][C:10]=2[NH:9][CH:8]=1

Participants

6

Reactant 4

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 89630048HCID 89630048, compound

Product 1

HCID 89630008HCID 89630008, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of N-(3-(5-(pyridin-2-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)methacrylamide (170 mg, 0.350 mmol) in dichloromethane (2.0 mL), was added CF3CO2H (2.0 mL). The resulting solution was stirred for 2 hours at 50° C. and then concentrated in vacuo. The residue was dissolved in methanol (2 mL), and ethane-1,2-diamine (42 mg, 0.70 mmol) and sodium hydroxide (98 mg, 1.6 mmol) were added. The resulting solution was stirred for 30 minutes at room temperature before being concentrated in vacuo. The resulting solution was extracted with ethyl acetate (×3) and the combined organic layers were washed with brine, dried with anhydrous sodium sulfate, filtered and concentrated in vacuo. Purification of the crude product by reverse phase HPLC using an acetonitrile gradient in water with 0.5% TFA modifier afforded N-(3-(5-(pyridin-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)methacrylamide as a white solid. LRMS (ESI) calc'd for C21H18N5O [M+H]+: 356, found 356. 1H NMR (400 MHz, CD3OD) δ 9.06 (s, 1H), 8.42 (d, J=5.6 Hz, 1H), 8.27 (s, 1H), 8.12-8.16 (m, 1H), 7.90 (s, 1H), 7.64-7.68 (m, 1H), 7.58 (d, J=8.0 Hz, 1H), 7.50 (d, J=6.8 Hz, 1H), 7.37-7.40 (m, 2H), 5.72 (s, 1H), 5.52 (s, 1H), 1.91 (s, 3H).

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in methanol (2 mL)
  3. stirringThe resulting solution was stirred for 30 minutes at room temperature
  4. concentrationbefore being concentrated in vacuo
  5. extractionThe resulting solution was extracted with ethyl acetate (×3)
  6. washthe combined organic layers were washed with brine
  7. dry with materialdried with anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification of the crude product by reverse phase HPLC

Sources & evidence

ORD record
ord-9d51f13ee75148bcbf7d1741b6d855d2
Source dataset
uspto-grants-2015_03
Patent number
US08993756B2

Reaction notes

Loading…