Potassium Carbonate → (S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-morpholinopyridin-4-yl)benzo[d]thiazol-6-yl)acetate

HRID 879428Notes

Reaction equation

HRID 879428 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:33]([CH3:34])=[CH:32][C:15]2[N:16]=[C:17]([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([N:25]4[CH2:30][CH2:29]N(C)[CH2:27][CH2:26]4)[CH:20]=3)[S:18][C:14]=2[C:13]=1OS(C(F)(F)F)(=O)=O)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].[Cl:43][C:44]1[CH:49]=[CH:48][C:47](B(O)O)=[CH:46][CH:45]=1.C(=O)([O-])[O-:54].[K+].[K+]>CC(OC)(C)C.COC1C=CC=C(OC)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].C(COC)OC.C(OCC)(=O)C>[C:1]([O:5][C@@H:6]([C:12]1[C:33]([CH3:34])=[CH:32][C:15]2[N:16]=[C:17]([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([N:25]4[CH2:26][CH2:27][O:54][CH2:29][CH2:30]4)[CH:20]=3)[S:18][C:14]=2[C:13]=1[C:47]1[CH:48]=[CH:49][C:44]([Cl:43])=[CH:45][CH:46]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 742994-Chlorophenylboronic acid2×HCID 131732631(S)-ethyl 2-tert-butoxy-2-(5-methyl-2-(2-(4-methylpiperazin-1-yl)pyridin-4-yl)-7-(trifluoromethylsulfonyloxy)benzo[d]thiazol-6-yl)acetate

Product 1

HCID 86700235(S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-morpholinopyridin-4-yl)benzo[d]thiazol-6-yl)acetate

Reagents, catalysts & solvents 3

HCID 71311105SPhos PalladacycleCatalyst2×HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of (S)-ethyl 2-tert-butoxy-2-(5-methyl-2-(2-(4-methylpiperazin-1-yl)pyridin-4-yl)-7-(trifluoromethylsulfonyloxy)benzo[d]thiazol-6-yl)acetate (20 mg, 0.0324 mmol), 4-chlorophenyboronic acid (10 mg, 0.063 mmol), SPhos precatalyst (3.3 mg, 0.0049 mmol) and powdered potassium carbonate (18 mg, 0.129 mmol) in anhydrous dimethoxyethane (0.75 mL) was sparged with nitrogen for 5 minutes, then heated in microwave at 120° C. for 1.5 h. Added more 4-chlorophenyboronic acid and SPhos precatalyst (3.3 mg, 0.0049 mmol) and continued reaction. Reaction mixture was diluted with ethyl acetate, washed with brine, dried (MgSO4), filtered, concentrated and purified by CombiFlash (0 to 40% EtOAc/Hex) to give product. LCMS-ESI+: calc'd for C31H35ClN3O4S: 580.2 (M+H+); Found: 580.3 (M+H+).

Workup

  1. customwas sparged with nitrogen for 5 minutes
  2. customreaction
  3. customReaction mixture
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by CombiFlash (0 to 40% EtOAc/Hex)
  9. customto give product

Sources & evidence

ORD record
ord-a5f6f03f816147c7bdc907438768fd53
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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