Cesium carbonate → Cyclopropanecarboxylic acid [2-(2-chloro-6-fluorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-yl]amide

HRID 626677노트

반응식

HRID 626677 반응식
Cl[C:2]1[C:7]2=[CH:8][N:9]([C:11]3[C:16]([F:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[N:10]=[C:6]2[CH:5]=[CH:4][N:3]=1.[CH:19]1([C:22]([NH2:24])=[O:23])[CH2:21][CH2:20]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:18][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]([F:17])[C:11]=1[N:9]1[CH:8]=[C:7]2[C:2]([NH:24][C:22]([CH:19]3[CH2:21][CH2:20]3)=[O:23])=[N:3][CH:4]=[CH:5][C:6]2=[N:10]1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 80376CyclopropanecarboxamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866970434-Chloro-2-(2-chloro-6-fluorophenyl)-2H-pyrazolo[4,3-c]pyridine

생성물 1

HCID 67701370Cyclopropanecarboxylic acid [2-(2-chloro-6-fluorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-yl]amide수율 43%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

실험 절차

A mixture of 4-chloro-2-(2-chloro-6-fluorophenyl)-2H-pyrazolo[4,3-c]pyridine (76 mg, 0.27 mmol), cyclopropylcarboxamide (26 mg, 0.31 mmol), Pd2(dba)3 (7 mg, 0.007 mmol), Xantphos (16 mg, 0.027 mmol) and cesium carbonate (176 mg, 0.54 mmol) in dioxane (2 mL) was sealed in a microwave vial, purged with nitrogen, and irradiated at 150° C. for 20 minutes in the microwave. The reaction mixture was cooled and partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (50% ethyl acetate in cyclohexane) to afford the title compound as a yellow solid (38 mg, 43% yield). 1H NMR (400 MHz, DMSO-d6): δ 11.15 (br s, 1H), 8.94 (s, 1H), 8.00 (d, J=6.3 Hz, 1H), 7.73 (td, J=8.3, 5.8 Hz, 1H), 7.67-7.66 (m, 1H), 7.64-7.52 (m, 2H), 7.36 (d, J=6.3 Hz, 1H), 2.18-2.12 (m, 1H), 0.93-0.86 (m, 4H). LCMS (Method B): RT=2.77 min, m/z: 331 [M+H+].

후처리

  1. customwas sealed in a microwave vial
  2. custompurged with nitrogen
  3. customirradiated at 150° C. for 20 minutes in the microwave
  4. temperatureThe reaction mixture was cooled
  5. custompartitioned between ethyl acetate and water
  6. washThe organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel flash chromatography (50% ethyl acetate in cyclohexane)

출처 및 근거

ORD 기록
ord-fd77e9d93e904aa8beaffcae4f84962d
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309240B2

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