Dimethylformamide → 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one

HRID 1056352Notes

Reaction equation

HRID 1056352 reaction equation
[C:1]([NH:5][C:6]1[C:7]([CH3:27])=[N:8][C:9]2[C:14]([N:15]=1)=[C:13]([C:16]1[NH:20][N:19]=[C:18]([C:21]([NH:23][CH2:24][CH2:25]Cl)=[O:22])[CH:17]=1)[CH:12]=[CH:11][CH:10]=2)([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].CN(C=O)C>C(#N)C>[C:1]([NH:5][C:6]1[C:7]([CH3:27])=[N:8][C:9]2[C:14]([N:15]=1)=[C:13]([C:16]1[CH:17]=[C:18]3[C:21](=[O:22])[NH:23][CH2:24][CH2:25][N:19]3[N:20]=1)[CH:12]=[CH:11][CH:10]=2)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 178432144HCID 178432144, compound

Product 1

HCID 897837742-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-oneYield 35.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
85 °C

Procedure

To a 10-mL reaction vial was added 5-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-N-(2-chloroethyl)-1H-pyrazole-3-carboxamide (471a) (82 mg, 0.21 mmol), K2CO3 (88 mg, 0.64 mmol), DMF (1 mL), and ACN (1 mL). The vial was closed and the reaction mixture was heated at 85° C. for 5 h. The reaction mixture was cooled to RT and partitioned between water (5 mL) and EtOAc (5 mL). The organic extract was taken and washed with brine (10 mL), dried over Na2SO4, and concentrated. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 0-3% 2 M NH3/MeOH in DCM to provide 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one (471) (26 mg, 35% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 13.51 (s, 1H), 7.86 (dd, J=1.27, 7.34 Hz, 1H), 7.75 (dd, J=1.08, 7.92 Hz, 1H), 7.36-7.42 (m, 2H), 6.07 (s, 1H), 4.36 (t, J=9.49 Hz, 2H), 3.90-3.97 (m, 2H), 2.56 (s, 3H), 1.51 (s, 9H). m/z (ESI, +ve) 351.0 (M+H)+.

Workup

  1. customTo a 10-mL reaction
  2. customThe vial was closed
  3. temperatureThe reaction mixture was cooled to RT
  4. custompartitioned between water (5 mL) and EtOAc (5 mL)
  5. extractionThe organic extract
  6. washwashed with brine (10 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customThe crude material was absorbed onto a plug of silica gel
  10. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (12 g)
  11. washeluting with a gradient of 0-3% 2 M NH3/MeOH in DCM

Sources & evidence

ORD record
ord-1c2cc76fa98b4e3485c9410896ab0e32
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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