Cesium carbonate → {6-[2-(2,6-Dichlorophenyl)-7-methoxy-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyrimidin-4-yl}-methanol

HRID 626740노트

반응식

HRID 626740 반응식
Br[C:2]1[C:7]2=[CH:8][N:9]([C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[N:10]=[C:6]2[C:5]([O:19][CH3:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[N:27]=[CH:26][N:25]=[C:24]([CH2:28][OH:29])[CH:23]=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]([Cl:17])[C:11]=1[N:9]1[CH:8]=[C:7]2[C:2]([NH:21][C:22]3[N:27]=[CH:26][N:25]=[C:24]([CH2:28][OH:29])[CH:23]=3)=[N:3][CH:4]=[C:5]([O:19][CH3:20])[C:6]2=[N:10]1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 21934615(6-Aminopyrimidin-4-yl)methanolHCID 866970604-Bromo-2-(2,6-dichlorophenyl)-7-methoxy-2H-pyrazolo[4,3-c]pyridine

생성물 1

HCID 69671394{6-[2-(2,6-Dichlorophenyl)-7-methoxy-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyrimidin-4-yl}-methanol수율 41.3%

시약·촉매·용매 2

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

실험 절차

A suspension of 4-bromo-2-(2,6-dichlorophenyl)-7-methoxy-2H-pyrazolo[4,3-c]pyridine (135 mg, 0.36 mmol), (6-aminopyrimidin-4-yl)methanol (50 mg, 0.4 mmol), Pd2(dba)3 (8 mg, 0.009 mmol), Xantphos (43 mg, 0.036 mmol) and cesium carbonate (235 mg, 0.72 mmol) in dioxane (3 mL) was sealed in a microwave vial, purged with nitrogen and irradiated at 150° C. for 1 hour 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 (0-2% methanol in ethyl acetate) to afford the title compound as a yellow solid (62 mg, 41% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.42 (s, 1H), 9.11 (s, 1H), 8.64 (d, J=0.9 Hz, 1H), 8.58 (d, J=1.2 Hz, 1H), 7.83 (d, J=1.3 Hz, 1H), 7.80 (s, 1H), 7.72 (dd, J=7.5, 9.2 Hz, 1H), 7.58 (s, 1H), 5.54 (t, J=6.0 Hz, 1H), 4.50 (d, J=6.0 Hz, 2H), 3.97 (s, 3H). LCMS (Method B): RT=2.75 min, m/z: 417 [M+H+].

후처리

  1. customwas sealed in a microwave vial
  2. custompurged with nitrogen
  3. customirradiated at 150° C. for 1 hour 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 (0-2% methanol in ethyl acetate)

출처 및 근거

ORD 기록
ord-922c49d06ae54776b72c48edff277dd8
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309240B2

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