Ethylenediamine → HCID 89630021, compound

HRID 882164Notes

Reaction equation

HRID 882164 reaction equation
[O:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[C:14]2[C:13]([C:15]3[CH:16]=[C:17]([NH:21][C:22](=[O:26])[C:23]([CH3:25])=[CH2:24])[CH:18]=[CH:19][CH:20]=3)=[N:12][CH:11]=[N:10][C:9]=2[N:8](COCC[Si](C)(C)C)[CH:7]=1.FC(F)(F)C(O)=O.C(N)CN.[OH-].[Na+]>ClCCl.CO>[O:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[C:14]2[C:13]([C:15]3[CH:16]=[C:17]([NH:21][C:22](=[O:26])[C:23]([CH3:25])=[CH2:24])[CH:18]=[CH:19][CH:20]=3)=[N:12][CH:11]=[N:10][C:9]=2[NH:8][CH:7]=1

Participants

7

Reactant 4

HCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 89615759HCID 89615759, compound

Product 1

HCID 89630021HCID 89630021, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To N-(3-(5-(oxazol-2-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)methacrylamide (140 mg, 0.295 mmol) was added portionwise, a solution of trifluoroacetic acid (3.4 g, 30 mmol) in dichloromethane (10 mL). The reaction was stirred for 1 hour at 50° C., then concentrated in vacuo. To this crude reaction mixture was added ethane-1,2-diamine (35 mg, 0.59 mmol), followed by portionwise addition of a solution of sodium hydroxide (82 mg, 2.1 mmol) in methanol (10 mL). After stirring at room temperature for 30 minutes, the reaction mixture was concentrated in vacuo and extracted with ethyl acetate (×3). 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-(oxazol-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl)methacrylamide as a green solid. LRMS (ESI) calc'd for C19H16N5O2 [M+H]+: 346, found 346. 1H NMR (400 MHz, CD3OD) δ 9.05 (s, 1H), 8.25 (s, 1H), 7.93 (s, 1H), 7.80 (d, 1H, J=8.0 Hz), 7.59 (s, 1H), 7.38-7.42 (m, 1H), 7.26 (d, J=8.0 Hz, 1H), 7.13 (s, 1H), 5.80 (s, 1H), 5.55 (s, 1H), 1.99 (s, 3H).

Workup

  1. concentrationconcentrated in vacuo
  2. customTo this crude reaction mixture
  3. stirringAfter stirring at room temperature for 30 minutes
  4. concentrationthe reaction mixture was concentrated in vacuo
  5. extractionextracted 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-68a1f799466c4106af17395fb32fe59d
Source dataset
uspto-grants-2015_03
Patent number
US08993756B2

Reaction notes

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