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 2069041Notes

Reaction equation

HRID 2069041 reaction equation
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

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 682631,1'-Carbonyldiimidazole2×HCID 29741323-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-amineHCID 585325744-(2-(4-Aminonaphthalen-1-yl)ethoxy)pyridin-2-amine

Product 1

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

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent3×

Procedure

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+).

Workup

  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

Sources & evidence

ORD record
ord-3f61dd3261d04cd581475df603e08176
Source dataset
uspto-grants-2012_10
Patent number
US08299073B2

Reaction notes

Loading…