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

HRID 879387Notes

Reaction equation

HRID 879387 reaction equation
Br[C:2]1[CH:3]=[C:4]2[CH:10]=[C:9]([CH3:11])[NH: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+].Br[C:39]1[S:40][C:41]2[C:47]([C:48]3[CH:53]=[CH:52][C:51]([Cl:54])=[CH:50][CH:49]=3)=[C:46]([C@H:55]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])[C:56]([O:58][CH2:59][CH3:60])=[O:57])[C:45]([CH3:66])=[CH:44][C:42]=2[N:43]=1.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:62]([O:61][C@@H:55]([C:46]1[C:45]([CH3:66])=[CH:44][C:42]2[N:43]=[C:39]([C:2]3[CH:3]=[C:4]4[CH:10]=[C:9]([CH3:11])[NH:8][C:5]4=[N:6][CH:7]=3)[S:40][C:41]=2[C:47]=1[C:48]1[CH:49]=[CH:50][C:51]([Cl:54])=[CH:52][CH:53]=1)[C:56]([O:58][CH2:59][CH3:60])=[O:57])([CH3:63])([CH3:64])[CH3:65]

Participants

10

Reactant 6

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 454896915-bromo-2-methyl-1H-pyrrolo[2,3-b]pyridineHCID 86700141(S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate

Product 1

HCID 86700195(S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)benzo[d]thiazol-6-yl)acetate

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

To a solution of 5-bromo-2-methyl-1H-pyrrolo[2,3-b]pyridine (85 mg, 0.403 mmol) in dioxane (4 mL) was added bis(pinacolato)diboron (123 mg, 0.483 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (33 mg, 0.040 mmol), potassium acetate (120 mg, 1.21 mmol). The mixture was degassed and heated at 100° C. for 2 h. The mixture was cooled, and then added (S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (100 mg, 0.201 mmol), tetrakis(triphenylphosphine)palladium(0) (24 mg, 0.02 mmol), K2CO3 (139 mg, 1.00 mmol) and water (1.3 mL, degassed). The reaction mixture was heated at 100° C. for 1 h, cooled and partitioned between ethyl acetate and brine. The organic layer was separated, dried over Na2SO4 and concentrated to give crude which was purified by chromatographic column to afford the desired product. LCMS-ESI+: calc'd for C30H30ClN3O3S: 548.3 (M+H+); Found: 548.3 (M+H+).

Workup

  1. customThe mixture was degassed
  2. temperatureThe mixture was cooled
  3. temperatureThe reaction mixture was heated at 100° 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. concentrationconcentrated
  9. customto give crude which
  10. customwas purified by chromatographic column

Sources & evidence

ORD record
ord-b52f284c01154493b61e7c813039460c
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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