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

HRID 626663

Reaction equation

HRID 626663 reaction equation
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

Participants

4

Reactant 2

HCID 6329Methylamine2×HCID 86697038(6-Chloropyrimidin-4-yl)-[2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine-4-yl]amine

Product 1

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

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

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+].

Workup

  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)

Sources & evidence

ORD record
ord-b973125bd98e46ff900de4068e40b2e0
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Linked notes

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