Tetrahydrofuran → 1-(4-(2-(2-Aminopyridin-4-yloxy)ethyl)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea

HRID 2069041노트

반응식

HRID 2069041 반응식
C1N=CN([C:6](N2C=NC=C2)=[O:7])C=1.[C:13]([C:17]1[CH:21]=[C:20]([NH2:22])[N:19]([C:23]2[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=2)[N:18]=1)([CH3:16])([CH3:15])[CH3:14].[NH2:30][C:31]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:34]([CH2:41][CH2:42][O:43][C:44]2[CH:49]=[CH:48][N:47]=[C:46]([NH2:50])[CH:45]=2)=[CH:33][CH:32]=1.C1COCC1>C(Cl)Cl.CO>[NH2:50][C:46]1[CH:45]=[C:44]([O:43][CH2:42][CH2:41][C:34]2[C:35]3[C:40](=[CH:39][CH:38]=[CH:37][CH:36]=3)[C:31]([NH:30][C:6]([NH:22][C:20]3[N:19]([C:23]4[CH:24]=[CH:25][C:26]([CH3:29])=[CH:27][CH:28]=4)[N:18]=[C:17]([C:13]([CH3:16])([CH3:15])[CH3:14])[CH:21]=3)=[O:7])=[CH:32][CH:33]=2)[CH:49]=[CH:48][N:47]=1

참가 물질

7

반응물 4

HCID 8028TetrahydrofuranHCID 682631,1'-Carbonyldiimidazole2회HCID 29741323-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-amineHCID 585325744-(2-(4-Aminonaphthalen-1-yl)ethoxy)pyridin-2-amine

생성물 1

HCID 585325361-(4-(2-(2-Aminopyridin-4-yloxy)ethyl)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea수율 52.4%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매3회

실험 절차

To a suspension of CDI (122 mg, 0.752 mmol) in DCM (2 mL) was added a solution of 3-tert-butyl-1-p-tolyl-1H-pyrazol-5-amine (172 mg, 0.752 mmol) in DCM (2.0 mL) and the reaction mixture was stirred at RT for 16 hr. An aliquot (1.0 mL) of this reaction mixture was added to a stirred suspension of 4-(2-(4-aminonaphthalen-1-yl)ethoxy)pyridin-2-amine (34) (42 mg, 0.150 mmol) in DCM (2.0 mL). THF (0.5 mL) was added and the reaction mixture was stirred for 1 hr. A second aliquot (1.0 mL) of the CDI reaction mixture was added and the mixture was stirred for a further 20 hr at RT. Methanol was added and stirring continued for 30 min. The solvent was evaporated and the residue was purified by flash column chromatography (SiO2, 0-5% MeOH in DCM, gradient elution). The resulting impure product was dissolved in ethyl acetate, washed with water and brine, dried (MgSO4) and evaporated in vacuo to afford the title compound (Intermediate F) (42 mg, 52%); m/z 535 (M+H)+, (ES+).

후처리

  1. stirringthe reaction mixture was stirred for 1 hr
  2. additionwas added
  3. stirringthe mixture was stirred for a further 20 hr at RT
  4. stirringstirring
  5. waitcontinued for 30 min
  6. customThe solvent was evaporated
  7. customthe residue was purified by flash column chromatography (SiO2, 0-5% MeOH in DCM, gradient elution)
  8. dissolutionThe resulting impure product was dissolved in ethyl acetate
  9. washwashed with water and brine
  10. dry with materialdried (MgSO4)
  11. customevaporated in vacuo

출처 및 근거

ORD 기록
ord-3f61dd3261d04cd581475df603e08176
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08299073B2

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