Sodium Carbonate → Methyl-4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-methylthiophene-2-carboxylate

HRID 1842606노트

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HRID 1842606 반응식
Br[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[C:9]([O:11][CH:12]([F:14])[F:13])[CH:8]=[N:7][C:6]=12.[CH3:15][O:16][C:17]([C:19]1[S:20][C:21]([CH3:33])=[C:22](B2OC(C)(C)C(C)(C)O2)[CH:23]=1)=[O:18].C(=O)([O-])[O-].[Na+].[Na+]>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.CN(C=O)C>[CH3:15][O:16][C:17]([C:19]1[S:20][C:21]([CH3:33])=[C:22]([C:2]2[CH:3]=[N:4][N:5]3[CH:10]=[C:9]([O:11][CH:12]([F:14])[F:13])[CH:8]=[N:7][C:6]=23)[CH:23]=1)=[O:18]

참가 물질

6

반응물 3

HCID 10340Sodium CarbonateHCID 46703107Methyl 5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxylateHCID 673254323-Bromo-6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidine

생성물 1

HCID 68304950Methyl-4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-methylthiophene-2-carboxylate수율 66.5%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매

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온도
85 °C

실험 절차

To a flask containing DMF (40.6 mL) was added 3-bromo-6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidine (1.07 g, 4.06 mmol), methyl-5-methyl-4-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolan-2-yl)-thiophene-2-carboxylate (1.20 g, 4.27 mmol), palladium tetrakis (235 mg, 0.203 mmol), and 2 M sodium carbonate (aq) (6.10 mL, 12.2 mmol). The reaction mixture was sealed and degassed with N2 for 5 min. The reaction mixture was then heated to 85° C. for 16 h. The reaction mixture was cooled to room temperature and diluted with dichloromethane. The organic layer was washed twice with saturated sodium bicarbonate (aq) twice and once with brine. The organic layer was dried with sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (0-80% EtOAc/Hex) to afford the title compound (0.916 g, 2.70 mmol). LRMS (APCI) calc'd for (C14H11F2N3O3S) [M+H]+, 340.1; found 340.0.

후처리

  1. customThe reaction mixture was sealed
  2. customdegassed with N2 for 5 min
  3. temperatureThe reaction mixture was cooled to room temperature
  4. additiondiluted with dichloromethane
  5. washThe organic layer was washed twice with saturated sodium bicarbonate (aq) twice
  6. dry with materialThe organic layer was dried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by column chromatography (0-80% EtOAc/Hex)

출처 및 근거

ORD 기록
ord-45802d7861a34d31931839b18a0970fc
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946237B2

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