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

HRID 1092026노트

반응식

HRID 1092026 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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 solid; 1H NMR (399.902 MHz, DMSO) δ 2.82 (t, J=5.1 Hz, 4H), 3.61 (t, J=4.8 Hz, 4H), 3.80 (s, 6H), 5.13 (s, 2H), 5.62 (bs, 1H), 6.50 (s, 1H), 6.65 (d, J=2.2 Hz, 2H), 6.92 (d, J=8.9 Hz, 1H), 8.09 (d, J=9.3 Hz, 1H), 8.76 (d, J=2.3 Hz, 1H), 10.74 (bs, 1H), 11.64 (bs, 1H). MS: m/z=439 (MH+)

후처리

  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

출처 및 근거

ORD 기록
ord-315abde425714b06ad3c5c6754b145a5
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129391B2

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