Acryloyl chloride → HCID 86679609, compound

HRID 577664Notes

Reaction equation

HRID 577664 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:31]=[CH:32][CH:33]=1)[O:5][C:6]1[C:7]2[C:21]([F:22])=[CH:20][N:19]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[C:8]=2[N:9]=[C:10]([NH:12][C:13]2[CH:17]=[CH:16][N:15]([CH3:18])[N:14]=2)[N:11]=1.[C:34](Cl)(=[O:37])[CH:35]=[CH2:36]>C(Cl)Cl>[F:22][C:21]1[C:7]2[C:6]([O:5][C:4]3[CH:3]=[C:2]([NH:1][C:34](=[O:37])[CH:35]=[CH2:36])[CH:33]=[CH:32][CH:31]=3)=[N:11][C:10]([NH:12][C:13]3[CH:17]=[CH:16][N:15]([CH3:18])[N:14]=3)=[N:9][C:8]=2[N:19]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:28])([CH3:29])[CH3:30])[CH:20]=1

Participants

4

Reactant 2

HCID 13140Acryloyl chloride3×HCID 86679610HCID 86679610, compound

Product 1

HCID 86679609HCID 86679609, compoundYield 55.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(3-aminophenoxy)-5-fluoro-N-(1-methyl-1H-pyrazol-3-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine (197 mg, 0.42 mmol) in DCM (20 mL) was added acryloyl chloride (34 μL, 0.42 mmol) and the reaction was stirred at rt for 45 min. Additional acryloyl chloride (34 μL, 0.42 mmol) was added and after another 2 hrs a final charge of acryloyl chloride (34 μL, 0.42 mmol) was added. After 30 min, the reaction was complete and was partitioned between DCM (30 mL) and saturated aqueous NaHCO3 (10 mL). The organic layer was separated, dried over Na2SO4 and evaporated to dryness. Purification via flash chromatography eluting with a gradient of 0%-80% EtOAc in heptane afforded the title compound (123 mg, 56 yield) as a solid. 1H NMR (400 MHz, methanol-d4) δ ppm 7.64 (s, 1H) 7.57 (d, J=8.81 Hz, 1H) 7.41 (t, J=8.18 Hz, 1H) 7.27 (d, J=1.76 Hz, 1H) 7.01 (dd, J=8.18, 2.14 Hz, 1H) 6.89 (d, J=2.27 Hz, 1H) 6.30-6.48 (m, 3H) 5.76 (dd, J=9.44, 2.14 Hz, 1H) 5.48 (s, 2H) 3.71 (s, 3H) 3.58 (t, J=8.06 Hz, 2H) 0.90 (t, J=8.06 Hz, 2H) −0.08 (s, 9H). m/z (APCI+) for C25H30FN7O3Si 524.2 (M+H)+.

Workup

  1. additionwas added
  2. waitAfter 30 min
  3. customwas partitioned between DCM (30 mL) and saturated aqueous NaHCO3 (10 mL)
  4. customThe organic layer was separated
  5. dry with materialdried over Na2SO4
  6. customevaporated to dryness
  7. customPurification via flash chromatography
  8. washeluting with a gradient of 0%-80% EtOAc in heptane

Sources & evidence

ORD record
ord-0a7558a23e044422ba051605cca9b85a
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Reaction notes

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