Dichloromethane → HCID 89629992, compound

HRID 882146Notes

Reaction equation

HRID 882146 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:14]2[C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][C:22](=[O:27])[C:23]([CH2:25]O)=[CH2:24])[CH:16]=3)=[N:12][CH:11]=[N:10][C:9]=2[NH:8][CH:7]=1)=[O:5])[CH3:2].C(Cl)Cl.CCN(S(F)(F)[F:37])CC>CS(C)=O>[CH2:1]([O:3][C:4]([C:6]1[C:14]2[C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][C:22](=[O:27])[C:23]([CH2:25][F:37])=[CH2:24])[CH:16]=3)=[N:12][CH:11]=[N:10][C:9]=2[NH:8][CH:7]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 123472(Diethylamino)sulfur trifluorideHCID 89630005HCID 89630005, compound

Product 1

HCID 89629992HCID 89629992, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To ethyl-4-(3-{[2-(hydroxymethyl)acryloyl]amino}phenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate (17 mg, 0.045 mmol) was added CH2Cl2 (0.90 mL) and the reaction was cooled to −78° C. before DAST (12 μL, 0.090 mmol) was added. The reaction was allowed to warm to room temperature over 2 hours. The reaction was quenched by pouring into a separatory funnel containing aqueous sodium bicarbonate (saturated) and was extracted with ethyl acetate (×3). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo to afford a residue that was dissolved in 2 mL of DMSO, and was purified by reverse phase HPLC using an acetonitrile gradient in water with 0.1% TFA modifier. Lyophilization of the desired fractions affords a colorless solid. LRMS (ESI) calc'd for C19H18N4O3F [M+H]+: 369, found 369. 1H NMR (600 MHz, DMSO-D6) δ 13.02 (bs, 1H), 10.25 (s, 114), 8.97 (s, 1H), 8.36 (m, 1H), 8.09 (s, 1H), 7.88 (d, 1H, J=7.8 Hz), 7.47 (t, 1H, J=7.8 Hz), 7.38 (d, 1H, J=7.8 Hz), 6.19 (s, 1H), 5.94 (s, 1H), 5.26 (s, 1H), 5.18 (s, 1H), 3.90 (q, 2H, J=7.2 Hz), 0.90 (t, 3H, J=7.2 Hz).

Workup

  1. additionwas added
  2. customThe reaction was quenched
  3. additionby pouring into a separatory funnel
  4. additioncontaining aqueous sodium bicarbonate (saturated)
  5. extractionwas extracted with ethyl acetate (×3)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto afford a residue that
  10. customwas purified by reverse phase HPLC
  11. customLyophilization of the desired fractions affords a colorless solid

Sources & evidence

ORD record
ord-b8ac1c84ee6a4cbfbc624539188d689f
Source dataset
uspto-grants-2015_03
Patent number
US08993756B2

Reaction notes

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