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

HRID 2356801

反応式

HRID 2356801 の反応式
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

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-a365d6159022483cb4e59b5445641195
出典データセット
uspto-grants-2010_07
特許番号
US07759376B2

関連ノート

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