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

HRID 16750Notes

Reaction equation

HRID 16750 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[CH: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]=[CH:44][C:43]([N:40]4[CH2:39][CH2:38][N:37]([CH3:36])[CH2:42][CH2:41]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 57440394Methyl 5-(4-methylpiperazin-1-yl)pyridine-2-carboxylateHCID 66589741Tert-butyl 5-amino-3-[(3,5-dimethoxyphenyl)methoxy]pyrazole-1-carboxylate

Product 1

HCID 66589730N-[5-[(3,5-Dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]-5-(4-methylpiperazin-1-yl)pyridine-2-carboxamideYield 67.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

NaHMDS (1M solution in THF, 0.45 ml, 0.451 mmol, 1.5 eq) was added dropwise to a stirred suspension of tert-butyl 5-amino-3-[(3,5-dimethoxyphenyl)methoxy]pyrazole-1-carboxylate (105 mg, 0.301 mmol, 1 eq) and methyl 5-(4-methylpiperazin-1-yl)pyridine-2-carboxylate (85 mg, 0.361 mmol, 1.2 eq) in dry THF (2.5 ml) under nitrogen. The solution was stirred at room temperature for 1 h. The solution was 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 reaction was repeated as above on a 0.338 mmol scale. The crude extracts were combined with those above and purified on by silica column chromatography, eluting with 0-6% MeOH in DCM, to afford the title compound as a pale brown solid (92 mg, 35% yield); 1H NMR (399.902 MHz, DMSO) δ 2.25 (s, 3H), 2.45-2.50 (m, 4H), 3.37-3.43 (m, 4H), 3.75 (s, 6H), 5.08 (s, 2H), 5.88 (bs, 1H), 6.45 (t, 1H), 6.60 (d, 2H), 7.45-7.49 (m, 1H), 7.94 (d, 1H), 8.35 (d, 1H), 10.89 (bs, 1H), 11.36 (bs, 1H) MS: m/z 453 (MH+)

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. custompurified on by silica column chromatography
  6. washeluting with 0-6% MeOH in DCM

Sources & evidence

ORD record
ord-4d1c1073f5ac4bfdb0686b043b4ad4af
Source dataset
uspto-grants-2010_06
Patent number
US07737149B2

Reaction notes

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