Sodium Bicarbonate → Methyl 3'-fluoro-4'-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-3-methylbiphenyl-4-carboxylate

HRID 2356801

Reaction equation

HRID 2356801 reaction equation
B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.Br[C:20]1[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[C:22]([CH3:30])[CH:21]=1.CC([O-])=O.[K+].Br[C:37]1[CH:42]=[CH:41][C:40]([NH:43][C:44]2[S:45][C:46]3[CH:52]=[C:51]([F:53])[CH:50]=[CH:49][C:47]=3[N:48]=2)=[C:39]([F:54])[CH:38]=1.C([O-])(O)=O.[Na+]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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>[F:54][C:39]1[CH:38]=[C:37]([C:20]2[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[C:22]([CH3:30])[CH:21]=2)[CH:42]=[CH:41][C:40]=1[NH:43][C:44]1[S:45][C:46]2[CH:52]=[C:51]([F:53])[CH:50]=[CH:49][C:47]=2[N:48]=1

Participants

9

Reactant 5

HCID 516892Sodium BicarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 7147089N-(4-bromo-2-fluorophenyl)-6-fluoro-1,3-benzothiazol-2-amineHCID 22031226Methyl 4-bromo-2-methylbenzoate

Product 1

HCID 59385264Methyl 3'-fluoro-4'-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-3-methylbiphenyl-4-carboxylate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

As shown in Reaction Scheme 6, a mixture of bis(pinacolato)diboron (0.55 g, 2.2 mmol), methyl 4-bromo-2-methylbenzoate (0.50 g, 2.2 mmol), palladium(II) acetate (0.01 g, 0.07 mmol), and KOAc (0.64 g, 6.6 mmol) in DMF (7.5 mL) was degassed with argon for 30 min at rt. The mixture was then heated at 80° C. for 4 h. After cooling the mixture to rt, N-(4-bromo-2-fluorophenyl)-6-fluoro-1,3-benzothiazol-2-amine (0.74 g, 2.2 mmol), tetrakis(triphenylphosphine)palladium(0) (0.08 g, 0.07 mmol), and saturated aqueous NaHCO3 (5 mL) were added. The mixture was heated at 85° C. overnight. The mixture was poured into ice water and extracted with EtOAc. The combined organic phases were dried over Na2SO4, concentrated in vacuo, and purified by column chromatography (20% EtOAc in hexanes). This yielded 0.345 g (39%) of the title compound. LC/MS m/z 411.3 (MH+; retention time 4.15 min. 1H NMR (400 MHz, CD2Cl2) 2.62 (s, 3H), 3.90 (s, 3H), 7.10 (t, 1H), 7.39-7.53 (m, 5H), 7.62-7.70 (m, 1H), 7.99 (d, 1H), 8.58 (t, 1H).

Workup

  1. customAs shown in Reaction Scheme 6
  2. customwas degassed with argon for 30 min at rt
  3. temperatureAfter cooling the mixture to rt
  4. temperatureThe mixture was heated at 85° C. overnight
  5. extractionextracted with EtOAc
  6. dry with materialThe combined organic phases were dried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. custompurified by column chromatography (20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-a365d6159022483cb4e59b5445641195
Source dataset
uspto-grants-2010_07
Patent number
US07759376B2

Linked notes

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