Bicarbonate Ion → HCID 54674065, compound

HRID 2362748Notes

Reaction equation

HRID 2362748 reaction equation
I[C:2]1[N:23](S(C2C=CC(C)=CC=2)(=O)=O)[C:5]2[N:6]=[CH:7][N:8]=[C:9]([C:10]3[S:14][C:13]([C:15]4([O:19]COC)[CH2:18][CH2:17][CH2:16]4)=[N:12][CH:11]=3)[C:4]=2[CH:3]=1.[CH3:34][N:35]1[CH:39]=[C:38](B2OC(C)(C)C(C)(C)O2)[CH:37]=[N:36]1.C(=O)(O)[O-]>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:34][N:35]1[CH:39]=[C:38]([C:2]2[NH:23][C:5]3[N:6]=[CH:7][N:8]=[C:9]([C:10]4[S:14][C:13]([C:15]5([OH:19])[CH2:16][CH2:17][CH2:18]5)=[N:12][CH:11]=4)[C:4]=3[CH:3]=2)[CH:37]=[N:36]1

Participants

6

Reactant 3

HCID 769Bicarbonate IonHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 67003660HCID 67003660, compound

Product 1

HCID 54674065HCID 54674065, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred ambient solution of 5-(6-iodo-7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-(1-(methoxymethoxy)cyclobutyl)thiazole (Example 160C) (60 mg, 0.10 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (25.0 mg, 0.120 mmol) in N,N-dimethylformamide (2.0 mL) was added saturated aqueous bicarbonate solution (1.0 mL) followed by bis(triphenylphosphine)palladium dichloride (7.02 mg, 10.0 μmol). The mixture was heated to 70° C. for 3 hours and was then quenched by the addition of water and ethyl acetate. The layers were separated, and the aqueous layer was extracted with additional ethyl acetate. The combined organics were dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was dissolved in methanol (1 mL), and 4 molar aqueous HCl solution (0.5 mL) was added. The reaction was heated to 60° C. for 2 hours and was then cooled to room temperature. 4 Normal aqueous sodium hydroxide solution (1 mL) was added, and the reaction heated to 80° C. for 1 hour. The reaction was cooled to room temperature, and the pH adjusted to ˜7 with 10% aqueous HCl solution. The aqueous layer was extracted with ethyl acetate (3×). The combined organics were dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The solid was triturated with diethyl ether to give the title compound. 1H NMR (500 MHz, DMSO-d6) ppm 1.76-2.08 (m, 2H) 2.31-2.45 (m, 2H) 2.54-2.66 (m, 2H) 3.93 (s, 3H) 6.62 (s, 1H) 7.24 (s, 1H) 8.11 (s, 1H) 8.29 (s, 1H) 8.65 (s, 1H) 8.69 (s, 1H) 12.58 (s, 1H); MS ESI(+) m/z 353 (M+H)+.

Workup

  1. customwas then quenched by the addition of water and ethyl acetate
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with additional ethyl acetate
  4. dry with materialThe combined organics were dried with anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residue was dissolved in methanol (1 mL)
  8. addition4 molar aqueous HCl solution (0.5 mL) was added
  9. temperatureThe reaction was heated to 60° C. for 2 hours
  10. temperaturewas then cooled to room temperature
  11. addition4 Normal aqueous sodium hydroxide solution (1 mL) was added
  12. temperaturethe reaction heated to 80° C. for 1 hour
  13. temperatureThe reaction was cooled to room temperature
  14. extractionThe aqueous layer was extracted with ethyl acetate (3×)
  15. dry with materialThe combined organics were dried with anhydrous sodium sulfate
  16. filtrationfiltered
  17. concentrationconcentrated under reduced pressure
  18. customThe solid was triturated with diethyl ether

Sources & evidence

ORD record
ord-0352f910cda449478cd1cc60b334b20f
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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