Ammonium Chloride → HCID 178492479, compound

HRID 1092028Notes

Reaction equation

HRID 1092028 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:48]=[CH:47][C:46]([C:49](OC)=[O:50])=[CH:45][N:44]=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[NH:15][N:16]=[C:12]([NH:11][C:49]([C:46]3[CH:47]=[N:48][C:43]([N:40]4[CH2:41][CH2:42][N:37]([CH3:36])[CH2:38][CH2:39]4)=[N:44][CH:45]=3)=[O:50])[CH:13]=2)[CH:27]=[C:28]([O:34][CH3:35])[CH:29]=1

Participants

7

Reactant 4

HCID 25517Ammonium Chloride2×HCID 2724254Sodium bis(trimethylsilyl)amide2×HCID 57440399Methyl 2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxylateHCID 66589741Tert-butyl 5-amino-3-[(3,5-dimethoxyphenyl)methoxy]pyrazole-1-carboxylate2×

Product 1

HCID 178492479HCID 178492479, compoundYield 14%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

NaHMDS (1M solution in THF, 0.39 ml, 0.386 mmol, 1.5 eq) was added dropwise to a stirred solution of tert-butyl 5-amino-3-[(3,5-dimethoxyphenyl)methoxy]pyrazole-1-carboxylate (90 mg, 0.258 mmol, 1 eq) and methyl 2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxylate (74 mg, 0.309 mmol, 1.2 eq) in dry THF (5 ml) under nitrogen. The solution was stirred at room is temperature for 1 h, then neutralised with satd. aq. NH4Cl, diluted with water (15 ml) and extracted with ethyl acetate (3×15 ml). The combined organic extracts were dried over MgSO4, filtered and evaporated to give an orange gum. The gum was purified by silica column chromatography, eluting with a gradient of 0-2.5% MeOH in DCM. The crude material, containing starting methyl 2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxylate, was re-dissolved in THF (5 ml) under nitrogen. tert-Butyl 5-amino-3-[(3,5-dimethoxyphenyl)methoxy]pyrazole-1-carboxylate (50 mg, 0.143 mmol) was added followed by dropwise addition of NaHMDS (1M solution in THF, 0.32 ml, 0.32 mmol). The solution was stirred at room temperature for 45 mins, neutralised with satd. aq. NH4Cl, diluted with water (10 ml) and extracted with ethyl acetate (3×10 ml). The combined organic extracts were dried over MgSO4, filtered and evaporated. The gummy residue was purified by silica column chromatography, eluting with a gradient of 0-8% MeOH in DCM, to afford the title compound as a pale brown solid (16 mg, 14% yield); 1H NMR (399.9 MHz, DMSO-d6+d4-AcOD) δ 2.42 (3H, s), 2.67-2.70 (4H, m), 3.75 (6H, s), 3.91-3.94 (4H, m), 5.08 (2H, s), 5.75 (1H, s), 6.45 (1H, t), 6.59 (2H, d), 8.90 (2H, s). MS: m/z 454 (MH+)

Workup

  1. customfor 1 h
  2. extractionextracted with ethyl acetate (3×15 ml)
  3. dry with materialThe combined organic extracts were dried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customto give an orange gum
  7. customThe gum was purified by silica column chromatography
  8. washeluting with a gradient of 0-2.5% MeOH in DCM
  9. additionThe crude material, containing
  10. dissolutionwas re-dissolved in THF (5 ml) under nitrogen
  11. stirringThe solution was stirred at room temperature for 45 mins
  12. extractionextracted with ethyl acetate (3×10 ml)
  13. dry with materialThe combined organic extracts were dried over MgSO4
  14. filtrationfiltered
  15. customevaporated
  16. customThe gummy residue was purified by silica column chromatography
  17. washeluting with a gradient of 0-8% MeOH in DCM

Sources & evidence

ORD record
ord-fad0003e454b4e359107d773bf073cfc
Source dataset
uspto-grants-2012_03
Patent number
US08129391B2

Reaction notes

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