Ammonium Chloride → N-[5-[(3,5-Dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]-5-(4-methylpiperazin-1-yl)pyrazine-2-carboxamide

HRID 1911304Notes

Reaction equation

HRID 1911304 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[NH2:11][C:12]1[N:16](C(OC(C)(C)C)=O)[N:15]=[C:14]([O:24][CH2:25][C:26]2[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=[C:28]([O:34][CH3:35])[CH:27]=2)[CH:13]=1.[CH3:36][N:37]1[CH2:42][CH2:41][N:40]([C:43]2[N:44]=[CH:45][C:46]([C:49](OC)=[O:50])=[N:47][CH:48]=2)[CH2:39][CH2:38]1.[NH4+].[Cl-]>C1COCC1.O>[CH3:33][O:32][C:30]1[CH:31]=[C:26]([CH2:25][O:24][C:14]2[CH:13]=[C:12]([NH:11][C:49]([C:46]3[CH:45]=[N:44][C:43]([N:40]4[CH2:41][CH2:42][N:37]([CH3:36])[CH2:38][CH2:39]4)=[CH:48][N:47]=3)=[O:50])[NH:16][N:15]=2)[CH:27]=[C:28]([O:34][CH3:35])[CH:29]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 57440384Methyl 5-(4-methylpiperazin-1-yl)pyrazine-2-carboxylateHCID 66589741Tert-butyl 5-amino-3-[(3,5-dimethoxyphenyl)methoxy]pyrazole-1-carboxylate

Product 1

HCID 66589890N-[5-[(3,5-Dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]-5-(4-methylpiperazin-1-yl)pyrazine-2-carboxamideYield 45.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

NaHMDS (1M solution in THF, 0.645 ml, 0.644 mmol, 1.5 eq) was added dropwise to a stirred suspension of tert-butyl 5-amino-3-[(3,5-dimethoxyphenyl)methoxy]pyrazole-1-carboxylate (150 mg, 0.429 mmol, 1 eq) and methyl 5-(4-methylpiperazin-1-yl)pyrazine-2-carboxylate (122 mg, 0.515 mmol, 1.2 eq) in dry THF (2.5 ml) under nitrogen. The reaction mixture was stirred at room temperature for 50 min, then neutralised with satd aq NH4Cl and diluted with water (5 ml). The aqueous phase was extracted with ethyl acetate (3×8 ml) and the combined organic extracts were dried over MgSO4, filtered and evaporated. The residual solid was purified by reverse-phase prep. HPLC using a gradient of 31-51% acetonitrile in water containing 1% ammonium hydroxide to afford the product as a white solid (88 mg, 45%).

Workup

  1. extractionThe aqueous phase was extracted with ethyl acetate (3×8 ml)
  2. dry with materialthe combined organic extracts were dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe residual solid was purified by reverse-phase prep

Sources & evidence

ORD record
ord-97f3adbfd60046c68eb89f6af876eb1c
Source dataset
uspto-grants-2013_12
Patent number
US08604022B2

Reaction notes

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