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Cesium carbonate → [2-(2,6-Dichloro-4-fluorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-yl]-(6-methylpyrimidin-4-yl)amine

HRID 626703
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HRID 626703 반응식
Cl[C:2]1[C:7]2=[CH:8][N:9]([C:11]3[C:16]([Cl:17])=[CH:15][C:14]([F:18])=[CH:13][C:12]=3[Cl:19])[N:10]=[C:6]2[CH:5]=[CH:4][N:3]=1.[CH3:20][C:21]1[N:26]=[CH:25][N:24]=[C:23]([NH2:27])[CH:22]=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:19][C:12]1[CH:13]=[C:14]([F:18])[CH:15]=[C:16]([Cl:17])[C:11]=1[N:9]1[CH:8]=[C:7]2[C:2]([NH:27][C:23]3[CH:22]=[C:21]([CH3:20])[N:26]=[CH:25][N:24]=3)=[N:3][CH:4]=[CH:5][C:6]2=[N:10]1
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참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 5728526-Methylpyrimidin-4-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866970484-Chloro-2-(2,6-dichloro-4-fluorophenyl)-2H-pyrazolo[4,3-c]pyridine

생성물 1

HCID 69671467[2-(2,6-Dichloro-4-fluorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-yl]-(6-methylpyrimidin-4-yl)amine수율 62%

시약·촉매·용매 2

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

실험 절차

A suspension of 4-chloro-2-(2,6-dichloro-4-fluorophenyl)-2H-pyrazolo[4,3-c]pyridine (70 mg, 0.22 mmol), 6-methylpyrimidin-4-ylamine (26 mg, 0.24 mmol), Pd2(dba)3 (10 mg, 0.011 mmol), Xantphos (12.8 mg, 0.022 mmol) and cesium carbonate (144 mg, 0.44 mmol) in dioxane (3 ml) was sealed in a microwave vial, purged with nitrogen and irradiated at 150° C. for 25 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 resultant residue was purified by silica gel flash chromatography (50-100% ethyl acetate in cyclohexane), then further triturated with diethyl ether:pentane (1:1) to afford the title compound as a yellow solid (53 mg, 62% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.65 (br s, 1H), 9.15 (s, 1H), 8.70 (s, 1H), 8.51 (s, 1H), 8.00 (d, J=6.4 Hz, 1H), 7.93 (d, J=8.4 Hz, 2H), 7.23 (d, J=6.4 Hz, 1H), 2.46 (s, 3H). LCMS (Method B): RT=2.94 min, m/z: 389 [M+H+].

후처리

  1. customwas sealed in a microwave vial
  2. custompurged with nitrogen
  3. customirradiated at 150° C. for 25 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 resultant residue was purified by silica gel flash chromatography (50-100% ethyl acetate in cyclohexane)
  10. customfurther triturated with diethyl ether:pentane (1:1)

출처 및 근거

ORD 기록
ord-a8194cbcee5441f6b41af39b5bac0d98
출처 데이터셋
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09309240B2

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