Potassium Carbonate → HCID 42601821, compound

HRID 2093532Notes

Reaction equation

HRID 2093532 reaction equation
[O:1]1[CH2:6][CH2:5][O:4][C:3]2[CH:7]=[C:8]([O:11][C:12]3[N:17]=[CH:16][N:15]=[C:14]([NH:18][C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([NH2:25])[N:20]=4)[CH:13]=3)[CH:9]=[CH:10][C:2]1=2.C(=O)([O-])[O-].[K+].[K+].[C:32](Cl)(=[O:35])[CH:33]=[CH2:34].C([O-])(O)=O.[Na+]>CN1C(=O)CCC1.O.CCN(CC)CC>[O:1]1[CH2:6][CH2:5][O:4][C:3]2[CH:7]=[C:8]([O:11][C:12]3[N:17]=[CH:16][N:15]=[C:14]([NH:18][C:19]4[N:20]=[C:21]([NH:25][C:32](=[O:35])[CH:33]=[CH2:34])[CH:22]=[CH:23][CH:24]=4)[CH:13]=3)[CH:9]=[CH:10][C:2]1=2

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 13140Acryloyl chlorideHCID 516892Sodium BicarbonateHCID 57708304HCID 57708304, compound

Product 1

HCID 42601821HCID 42601821, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8471TriethylamineSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of N2-(6-(2,3-dihydrobenzo[b][1,4]dioxin-6-yloxy)pyrimidin-4-yl)pyridine-2,6-diamine (0.080 g, 0.23 mmol) and potassium carbonate (0.065 g, 0.47 mmol) in NMP (0.8 mL) at 0° C. was added acryloyl chloride (0.026 g, 0.29 mmol) and the reaction mixture was stirred at 0° C. for 30 min. The reaction mixture was added dropwise to a cold, stifling solution of 10% NaHCO3 and was stirred at 0° C. for 30 min. A white solid was isolated by filtration. The solid was washed with cold water and hexane and dissolved in a 2 mL of methanol/dichloromethane (1/1). This solution was concentrated under reduced pressure. The residue obtained was suspended in cold water (5 mL), Et3N was added to it and it was extracted with ethyl acetate (2×5 mL). The combined ethyl acetate extract was washed with water (2 mL) and brine (2 mL), was dried over Na2SO4 and was concentrated under reduced pressure to obtain N-(6-(6-(2,3-dihydrobenzo[b][1,4]dioxin-6-yloxy)pyrimidin-4-ylamino)pyridin-2-yl)acrylamide (I-95) as a light yellow solid. 1H NMR (DMSO-d6) δ ppm: 4.25 (s, 4H), 5.79 (dd, J=1.84 & 10.08 Hz, 1H), 6.30 (dd, J=1.84 & 16.96 Hz, 1H), 6.62-6.72 (m, 3H), 6.88 (d, J=8.72 Hz, 1H), 7.03 (d, J=7.84 Hz, 1H), 7.69 (t, J=7.96 Hz, 1H), 7.70 (d, J=7.84 Hz, 1H), 7.85 (s, 1H), 8.32 (d, J=0.4 Hz, 1H), 10.16 (s, 1H), 10.47 (s, 1H); LCMS: m/e 392.

Workup

  1. additionThe reaction mixture was added dropwise to a cold,
  2. stirringwas stirred at 0° C. for 30 min
  3. customA white solid was isolated by filtration
  4. washThe solid was washed with cold water and hexane
  5. dissolutiondissolved in a 2 mL of methanol/dichloromethane (1/1)
  6. concentrationThis solution was concentrated under reduced pressure
  7. customThe residue obtained
  8. extractionwas extracted with ethyl acetate (2×5 mL)
  9. extractionThe combined ethyl acetate extract
  10. washwas washed with water (2 mL) and brine (2 mL)
  11. dry with materialwas dried over Na2SO4
  12. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-c42e7a597c574f62939cd280189b857b
Source dataset
uspto-grants-2013_05
Patent number
US08445498B2

Reaction notes

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