Hydrochloric Acid → N-[5-[(3,5-Dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]-6-piperazin-1-yl-pyridine-3-carboxamide

HRID 16755

Reaction equation

HRID 16755 reaction equation
CC(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:19]=[CH:18][C:17]([C:20]([OH:22])=O)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=O)(C)C.ClC(N(C)C)=C(C)C.N1C=CC=CC=1.[NH2:37][C:38]1[N:42](C(OC(C)(C)C)=O)[N:41]=[C:40]([O:50][CH2:51][C:52]2[CH:57]=[C:56]([O:58][CH3:59])[CH:55]=[C:54]([O:60][CH3:61])[CH:53]=2)[CH:39]=1.Cl.O1CCOCC1>C1COCC1>[CH3:59][O:58][C:56]1[CH:57]=[C:52]([CH2:51][O:50][C:40]2[CH:39]=[C:38]([NH:37][C:20]([C:17]3[CH:18]=[N:19][C:14]([N:11]4[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]4)=[CH:15][CH:16]=3)=[O:22])[NH:42][N:41]=2)[CH:53]=[C:54]([O:60][CH3:61])[CH:55]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 312751,4-DioxaneHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 27718236-(4-((Tert-butoxy)carbonyl)piperazin-1-yl)pyridine-3-carboxylic acidHCID 66589741Tert-butyl 5-amino-3-[(3,5-dimethoxyphenyl)methoxy]pyrazole-1-carboxylate

Product 1

HCID 66589835N-[5-[(3,5-Dimethoxyphenyl)methoxy]-2H-pyrazol-3-yl]-6-piperazin-1-yl-pyridine-3-carboxamideYield 26%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

6-[4-[(2-Methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]pyridine-3-carboxylic acid (150 mg, 0.412 mmol) was dissolved in dry THF (10 ml), 1-chloro-N,N,2-trimethyl-prop-1-en-1-amine (65 μl, 0.412 mmol) was added and the mixture was stirred at room temperature under nitrogen overnight. Pyridine (40 μl, 0.412 mmol) and tert-butyl 5-amino-3-[(3,5-dimethoxyphenyl)methoxy]pyrazole-1-carboxylate (142 mg, 0.343 mmol) were added and the mixture was stirred at 65° C. for 18 h. The mixture was then cooled to room temperature and stirred overnight with 4 M HCl in dioxane (1.8 ml, 7.20 mmol). The mixture was then filtered and the solid was washed with hexane. The product was purified on acidic prep. HPLC, eluting with a gradient of 16-26% MeCN in water (containing 0.1% TFA). The product containing fractions were neutralised with aq. NaHCO3 and the acetonitrile removed under vacuum. The product precipitated out and was collected by filtration. This was further washed with water and dried in vacuo to give the title compound (39 mg, 26%) as a white

Workup

  1. stirringthe mixture was stirred at 65° C. for 18 h
  2. temperatureThe mixture was then cooled to room temperature
  3. filtrationThe mixture was then filtered
  4. washthe solid was washed with hexane
  5. customThe product was purified on acidic prep
  6. washHPLC, eluting with a gradient of 16-26% MeCN in water (containing 0.1% TFA)
  7. additionThe product containing fractions
  8. customthe acetonitrile removed under vacuum
  9. customThe product precipitated out
  10. filtrationwas collected by filtration
  11. washThis was further washed with water
  12. customdried in vacuo

Sources & evidence

ORD record
ord-08874572a0e14e979fa38b435692c740
Source dataset
uspto-grants-2010_06
Patent number
US07737149B2

Linked notes

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