Cesium carbonate → N-[2-(2,6-Dichlorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-yl]-pyridazine-3,6-diamine

HRID 626668노트

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HRID 626668 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[CH:18]=[C:12]2[C:13]([NH2:17])=[N:14][CH:15]=[CH:16][C:11]2=[N:10]1.[NH2:19][C:20]1[N:21]=[N:22][C:23](Cl)=[CH:24][CH:25]=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:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[CH:18]=[C:12]2[C:13]([NH:17][C:23]3[N:22]=[N:21][C:20]([NH2:19])=[CH:25][CH:24]=3)=[N:14][CH:15]=[CH:16][C:11]2=[N:10]1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 216436-Amino-3-chloropyridazineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 696711782-(2,6-Dichlorophenyl)-2h-pyrazolo[4,3-c]pyridin-4-amine

생성물 1

HCID 69671267N-[2-(2,6-Dichlorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-yl]-pyridazine-3,6-diamine수율 13%

시약·촉매·용매 2

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

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온도
150 °C

실험 절차

A mixture of 2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine-4-ylamine (100 mg, 0.36 mmol), 3-amino-6-chloropyridazine (57 mg, 0.44 mmol), Pd2(dba)3 (8 mg, 0.009 mmol), Xantphos (21 mg, 0.036 mmol) and cesium carbonate (234 mg, 0.72 mmol) in dioxane (2.5 mL) was degassed with argon then heated at 150° C. for 30 minutes in a microwave reactor. The reaction mixture was 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 (4-7% methanol in DCM) to afford the title compound as a beige solid (17 mg, 13% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.45 (d, J=0.9 Hz, 1H), 7.95-7.89 (m, 2H), 7.86-7.84 (m, 2H), 7.76 (dd, J=9.1, 7.2 Hz, 1H), 7.62 (d, J=9.7 Hz, 1H), 7.57-7.53 (m, 1H). LCMS (Method B): RT=2.56 min, m/z: 372 [M+H+].

후처리

  1. customwas degassed with argon
  2. customThe reaction mixture was partitioned between ethyl acetate and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel flash chromatography (4-7% methanol in DCM)

출처 및 근거

ORD 기록
ord-4ffbbf21ed944cf2b1333169b1326a5b
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309240B2

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