Sodium Carbonate → HCID 59627653, 화합물

HRID 1930161노트

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HRID 1930161 반응식
[C:1]([C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=2)[C:7]([CH3:19])=[N:6][C:5]=1[CH3:20])(=[O:3])[NH2:2].[F:21][C:22]1[CH:23]=[C:24]([CH:37]([CH3:42])[C:38]([O:40][CH3:41])=[O:39])[CH:25]=[C:26]([F:36])[C:27]=1OS(C(F)(F)F)(=O)=O.C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Li+]>COCCOC.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>[C:1]([C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:27]3[C:26]([F:36])=[CH:25][C:24]([CH:37]([CH3:42])[C:38]([O:40][CH3:41])=[O:39])=[CH:23][C:22]=3[F:21])=[CH:12][CH:11]=2)[C:7]([CH3:19])=[N:6][C:5]=1[CH3:20])(=[O:3])[NH2:2]

참가 물질

7

반응물 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 59627637HCID 59627637, 화합물2회HCID 596277414-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)phenylboronic acid

생성물 1

HCID 59627653HCID 59627653, 화합물수율 67.6%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 80711,2-Dimethoxyethane용매

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온도
85 °C

실험 절차

A solution of 4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)phenylboronic acid (175 mg, 0.65 mmol) and methyl 2-(3,5-difluoro-4-(trifluoromethylsulfonyloxy)phenyl)propanoate (Intermediate 21-2; 200 mg, 0.57 mmol) and Sodium carbonate (0.467 mL, 0.93 mmol), tetrakis(triphenylphosphine)palladium(0) (41.1 mg, 0.04 mmol) and lithium chloride (42.6 mg, 1.01 mmol) in DME (14.300 mL) was degassed and then stirred at 85° C. for 17 hours. The reaction mixture was partitioned between EtOAc (10 mL) and saturated brine (15 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford methyl 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2,6-difluorobiphenyl-4-yl)propanoate (164 mg, 67.1%) as a white solid.

후처리

  1. customThe reaction mixture was partitioned between EtOAc (10 mL) and saturated brine (15 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customto afford crude product
  6. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane
  7. customPure fractions were evaporated to dryness

출처 및 근거

ORD 기록
ord-d78c107465614ad0aaed448ddab93a9d
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188092B2

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