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

HRID 879393Notes

Reaction equation

HRID 879393 reaction equation
Br[C:2]1[N:7]=[C:6]2[N:8]([CH3:12])[CH:9]=[C:10]([CH3:11])[C:5]2=[CH:4][CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.ClCCl.C([O-])(=O)C.[K+].[C:39]([O:43][C@H:44]([C:50]1[C:65]([CH3:66])=[CH:64][C:53]2[N:54]=[C:55]([C:57]3[CH:62]=[CH:61][N:60]=[C:59](Cl)[CH:58]=3)[S:56][C:52]=2[C:51]=1[C:67]1[CH:72]=[CH:71][C:70]([Cl:73])=[CH:69][CH:68]=1)[C:45]([O:47][CH2:48][CH3:49])=[O:46])([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:39]([O:43][C@@H:44]([C:50]1[C:65]([CH3:66])=[CH:64][C:53]2[N:54]=[C:55]([C:57]3[CH:62]=[CH:61][N:60]=[C:59]([C:3]4[CH:4]=[C:5]5[C:10]([CH3:11])=[CH:9][N:8]([CH3:12])[C:6]5=[N:7][CH:2]=4)[CH:58]=3)[S:56][C:52]=2[C:51]=1[C:67]1[CH:68]=[CH:69][C:70]([Cl:73])=[CH:71][CH:72]=1)[C:45]([O:47][CH2:48][CH3:49])=[O:46])([CH3:40])([CH3:41])[CH3:42]

Participants

10

Reactant 6

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 867001976-bromo-1,3-dimethyl-1H-pyrrolo[2,3-b]pyridineHCID 86700200(R)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(2-chloropyridin-4-yl)-5-methylbenzo[d]thiazol-6-yl)acetate

Product 1

HCID 86700199(S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(2-(1,3-dimethyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyridine-4-yl)-5-methylbenzo[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 6-bromo-1,3-dimethyl-1H-pyrrolo[2,3-b]pyridine (15 mg, 0.067 mmol) in dioxane (1 mL) was added bis(pinacolato)diboron (20 mg, 0.080 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (5.5 mg, 0.0067 mmol), potassium acetate (20 mg, 0.201 mmol). The mixture was degassed and heated at 100° C. for 2 h. The mixture was cooled, and then added (R)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-2-(2-chloropyridin-4-yl)-5-methylbenzo[d]thiazol-6-yl)acetate (24 mg, 0.045 mmol), tetrakis(triphenylphosphine)palladium(0) (5 mg, 0.0045 mmol), K2CO3 (31 mg, 0.227 mmol) and water (0.3 mL, degassed). The reaction mixture was heated at 110° 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 C36H35ClN4O3S: 639.3 (M+H+); Found: 639.3 (M+H+).

Workup

  1. customThe mixture was degassed
  2. temperatureThe mixture was cooled
  3. temperatureThe reaction mixture was heated at 110° 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-b57112b55df74f6ab825ab49386abab2
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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