Methylamine → N-[2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine-4-yl]-N'-methylpyrimidine-4,6-diamine

HRID 626663

반응식

HRID 626663 반응식
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[C:14]3=[CH:15][N:16]([C:18]4[C:23]([Cl:24])=[CH:22][CH:21]=[CH:20][C:19]=4[Cl:25])[N:17]=[C:13]3[CH:12]=[CH:11][N:10]=2)[CH:3]=1.[CH3:26][NH2:27]>CN1C(=O)CCC1>[Cl:24][C:23]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:25])[C:18]=1[N:16]1[CH:15]=[C:14]2[C:9]([NH:8][C:4]3[CH:3]=[C:2]([NH:27][CH3:26])[N:7]=[CH:6][N:5]=3)=[N:10][CH:11]=[CH:12][C:13]2=[N:17]1

참가 물질

4

반응물 2

HCID 6329Methylamine2회HCID 86697038(6-Chloropyrimidin-4-yl)-[2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine-4-yl]amine

생성물 1

HCID 69671122N-[2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine-4-yl]-N'-methylpyrimidine-4,6-diamine수율 45.3%

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

A solution of (6-chloropyrimidin-4-yl)-[2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine-4-yl]amine (80 mg, 0.20 mmol) and methylamine (2M in THF, 300 μL, 0.60 mmol) in NMP (2.0 mL) was sealed in a microwave vial, purged with nitrogen and irradiated at 160° C. for 30 minutes in the microwave. Further methylamine (300 μL, 0.20 mmol) was added and the reaction mixture was irradiated at 170° C. for 30 minutes. The resultant 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 (4-5% methanol in DCM) to afford the title compound as a white solid (35.0 mg, 45% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.03 (br s, 1H), 9.14 (s, 1H), 8.21 (s, 1H), 7.91 (d, J=6.3 Hz, 1H), 7.80 (d, J=8.1 Hz, 2H), 7.70 (dd, J=9.0, 7.4 Hz, 1H), 7.23 (br s, 1H), 7.13 (d, J=6.4 Hz, 1H), 2.81 (d, J=4.7 Hz, 3H). LCMS (Method B): RT=2.99 min, m/z: 386 [M+H+].

후처리

  1. custompurged with nitrogen
  2. customirradiated at 160° C. for 30 minutes in the microwave
  3. customthe reaction mixture was irradiated at 170° C. for 30 minutes
  4. custompartitioned between ethyl acetate and water
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel flash chromatography (4-5% methanol in DCM)

출처 및 근거

ORD 기록
ord-b973125bd98e46ff900de4068e40b2e0
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309240B2

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