Dichloromethane → (S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(1-methyl-1H-pyrazolo[4,3-b]pyridine-6-yl)benzo[d]thiazol-6-yl)ethyl pivalate

HRID 879297Notes

Reaction equation

HRID 879297 reaction equation
Br[C:2]1[CH:3]=[C:4]2[N:10]([CH3:11])[N:9]=[CH:8][C:5]2=[N:6][CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.ClCCl.C([O-])(=O)C.[K+].[C:38]([O:44][CH2:45][C@H:46]([C:52]1[C:61]([CH3:62])=[CH:60][C:55]2[N:56]=[C:57](Br)[S:58][C:54]=2[C:53]=1[C:63]1[CH:68]=[CH:67][C:66]([Cl:69])=[CH:65][CH:64]=1)[O:47][C:48]([CH3:51])([CH3:50])[CH3:49])(=[O:43])[C:39]([CH3:42])([CH3:41])[CH3:40].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[C:38]([O:44][CH2:45][C@@H:46]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])[C:52]1[C:61]([CH3:62])=[CH:60][C:55]2[N:56]=[C:57]([C:2]3[CH:3]=[C:4]4[N:10]([CH3:11])[N:9]=[CH:8][C:5]4=[N:6][CH:7]=3)[S:58][C:54]=2[C:53]=1[C:63]1[CH:64]=[CH:65][C:66]([Cl:69])=[CH:67][CH:68]=1)(=[O:43])[C:39]([CH3:41])([CH3:40])[CH3:42]

Participants

10

Reactant 6

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 401522616-Bromo-1-methyl-1H-pyrazolo(4,3-b)pyridineHCID 86699799(S)-2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyethyl pivalate

Product 1

HCID 86699816(S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(1-methyl-1H-pyrazolo[4,3-b]pyridine-6-yl)benzo[d]thiazol-6-yl)ethyl pivalate

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 6-bromo-1-methyl-1H-pyrazolo[4,3-b]pyridine (20 mg, 0.094 mmol) in dioxane (2 mL) was added bis(pinacolato)diboron (29 mg, 0.113 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (8 mg, 0.0094 mmol), potassium acetate (19 mg, 0.189 mmol). The mixture was degassed and heated at 100° C. for 2 h. The mixture was cooled, and then added (S)-2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyethyl pivalate (25 mg, 0.046 mmol), tetrakis(triphenylphosphine)palladium(0) (6 mg, 0.005 mmol), K2CO3 (33 mg, 0.23 mmol) and water (0.3 mL, degassed). The reaction mixture was heated at 90° C. for 1 h, cooled and partitioned between ethyl acetate and brine. The organic layer was separated, dried over Na2SO4, filtered and concentrated to give crude product which was purified by chromatographic column to afford the desired product. LCMS-ESI+: calc'd for C32H35ClN4O3S: 591.22 (M+H+); Found: 591.2 (M+H+).

Workup

  1. customThe mixture was degassed
  2. temperatureThe mixture was cooled
  3. temperatureThe reaction mixture was heated at 90° C. for 1 h
  4. temperaturecooled
  5. custompartitioned between ethyl acetate and brine
  6. customThe organic layer was separated
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give crude product which
  11. customwas purified by chromatographic column

Sources & evidence

ORD record
ord-d05fba42188d4cc19bf61b698c34e9f0
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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