Dimethylacetamide → 2-(2,6-Dichlorophenyl)-4-(6-methylpyrimidin-4-ylamino)-2H-pyrazolo[4,3-c]pyridine-7-carbonitrile

HRID 626735Notes

Reaction equation

HRID 626735 reaction equation
Br[C:2]1[C:3]2[C:4](=[CH:16][N:17]([C:19]3[C:24]([Cl:25])=[CH:23][CH:22]=[CH:21][C:20]=3[Cl:26])[N:18]=2)[C:5]([NH:8][C:9]2[CH:14]=[C:13]([CH3:15])[N:12]=[CH:11][N:10]=2)=[N:6][CH:7]=1.C[C:28]([N:30](C)C)=O>[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:26][C:20]1[CH:21]=[CH:22][CH:23]=[C:24]([Cl:25])[C:19]=1[N:17]1[CH:16]=[C:4]2[C:5]([NH:8][C:9]3[CH:14]=[C:13]([CH3:15])[N:12]=[CH:11][N:10]=3)=[N:6][CH:7]=[C:2]([C:28]#[N:30])[C:3]2=[N:18]1

Participants

5

Reactant 2

HCID 31374DimethylacetamideHCID 69671843[7-Bromo-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-yl]-(6-methylpyrimidin-4-yl)-amine

Product 1

HCID 696713182-(2,6-Dichlorophenyl)-4-(6-methylpyrimidin-4-ylamino)-2H-pyrazolo[4,3-c]pyridine-7-carbonitrileYield 17%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

A suspension of [7-bromo-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-yl]-(6-methylpyrimidin-4-yl)-amine (100 mg, 0.22 mmol), Zn(CN)2 (52 mg, 0.44 mmol), and Pd(PPh3)4 (25 mg, 0.022 mmol), in DMA (1.0 mL) was sealed in a microwave vial, purged with nitrogen, and irradiated in a microwave reactor at 150° C. for 30 minutes. 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 (0-70% ethyl acetate in cyclohexane), to afford the title compound as an off-white solid (15 mg, 17% yield). 1H NMR (400 MHz, DMSO-d6): δ 11.32 (br s, 1H), 9.36 (s, 1H), 8.80 (d, J=1.0 Hz, 1H), 8.61 (s, 1H), 8.46 (s, 1H), 7.86 (d, J=1.0 Hz, 1H), 7.83 (s, 1H), 7.74 (dd, J=7.4, 1.8 Hz, 1H), 2.50 (s, 3H). LCMS (Method B): RT=3.84 min, m/z: 396 [M+H+].

Workup

  1. custompurged with nitrogen
  2. customirradiated in a microwave reactor at 150° C. for 30 minutes
  3. temperatureThe reaction mixture was cooled
  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 resultant residue was purified by silica gel flash chromatography (0-70% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-4dceda6478fd4012baf05d02a5aacc49
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

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