Bicarbonate Ion → HCID 54672778, compound

HRID 2362667Notes

Reaction equation

HRID 2362667 reaction equation
[Cl:1][C:2]1[C:3]([C:22]2[S:26][C:25]([C:27]3([OH:31])[CH2:30][CH2:29][CH2:28]3)=[N:24][CH:23]=2)=[C:4]2[CH:10]=[C:9](I)[N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]2=[N:6][CH:7]=1.[C:32]([C:34]1[CH:35]=[C:36](B(O)O)[CH:37]=[CH:38][CH:39]=1)#[N:33].C(=O)(O)[O-].[Mg].[Cl-].[NH4+]>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>[Cl:1][C:2]1[C:3]([C:22]2[S:26][C:25]([C:27]3([OH:31])[CH2:28][CH2:29][CH2:30]3)=[N:24][CH:23]=2)=[C:4]2[CH:10]=[C:9]([C:38]3[CH:39]=[C:34]([CH:35]=[CH:36][CH:37]=3)[C:32]#[N:33])[NH:8][C:5]2=[N:6][CH:7]=1

Participants

8

Reactant 5

HCID 769Bicarbonate IonHCID 25517Ammonium ChlorideHCID 27343253-Cyanophenylboronic acidHCID 5462224MagnesiumHCID 67003374HCID 67003374, compound

Product 1

HCID 54672778HCID 54672778, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred ambient solution of 1-(5-(5-chloro-2-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutanol (Example 8A) (50 mg, 0.085 mmol) and 3-cyanophenylboronic acid (18.8 mg, 0.128 mmol) in N,N-dimethylformamide (2.0 mL) was added saturated aqueous bicarbonate solution (683 μl) followed by bis(triphenylphosphine)palladium dichloride (4.2 mg, 6.0 μmol). The mixture was heated to 70° C. for 4 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 (2 mL). Magnesium turnings (20.7 mg, 0.853 mmol) and solid ammonium chloride (18.26 mg, 0.341 mmol) were added, and the mixture stirred vigorously for 16 hours. The reaction was partitioned between ethyl acetate and saturated aqueous bicarbonate solution. 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 purified by reverse phase high performance liquid chromatography (RP HPLC, 19×150 mm Atlantis Prep T3 OBD m column, eluting with a gradient of 5% B in A to 75% B in A over 25 minutes, wherein A is water containing 0.1% v/v trifluoroacetic acid and B is acetonitrile containing 0.1% v/v trifluoroacetic acid). The fractions containing the product were diluted with ethyl acetate and washed with saturated aqueous bicarbonate solution. The ethyl acetate solution was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the title compound. 1H NMR (500 MHz, DMSO-d6) δ 12.71 (s, 1H), 8.57 (bs, 1H), 8.39 (s, 1H), 8.35 (d, J=8.4 Hz, 1H), 8.30 (s, 1H), 7.83 (d, J=7.7 Hz, 1H), 7.70-7.67 (m, 1H), 7.35 (bs, 1H), 6.70 (s, 2H), 2.68-2.59 (m, 2H), 2.46-2.38 (m, 2H), 2.06-1.89 (m, 2H); MS ESI(+) m/z 406.9 [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 (2 mL)
  8. customThe reaction was partitioned between ethyl acetate and saturated aqueous bicarbonate solution
  9. customThe layers were separated
  10. extractionthe aqueous layer was extracted with additional ethyl acetate
  11. dry with materialThe combined organics were dried with anhydrous sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by reverse phase high performance liquid chromatography (RP HPLC, 19×150 mm Atlantis Prep T3 OBD m column
  15. washeluting with a gradient of 5% B in A to 75% B in A over 25 minutes
  16. additionThe fractions containing the product
  17. additionwere diluted with ethyl acetate
  18. washwashed with saturated aqueous bicarbonate solution
  19. dry with materialThe ethyl acetate solution was dried with anhydrous sodium sulfate
  20. filtrationfiltered
  21. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-bede5a3dee64442e96632c97da7dfe9b
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

Loading…