Diisopropylethylamine → 1-(4-(2-(3-aminopyridin-4-yl)ethoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea

HRID 1916805Notes

Reaction equation

HRID 1916805 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([N:10]=[C:11]=[O:12])[N:7]([C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:20][C:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24]([O:31][CH2:32][CH2:33][C:34]2[CH:39]=[CH:38][N:37]=[CH:36][C:35]=2[NH2:40])=[CH:23][CH:22]=1.CCN(C(C)C)C(C)C>C1COCC1.CC#N.[Cl-].[Na+].O>[NH2:40][C:35]1[CH:36]=[N:37][CH:38]=[CH:39][C:34]=1[CH2:33][CH2:32][O:31][C:24]1[C:25]2[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:21]([NH:20][C:11]([NH:10][C:8]2[N:7]([C:13]3[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=3)[N:6]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[CH:9]=2)=[O:12])=[CH:22][CH:23]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 179878553-tert-Butyl-5-isocyanato-1-p-tolyl-1H-pyrazoleHCID 584167794-(2-(4-Aminonaphthalen-1-yloxy)ethyl)pyridin-3-amine

Product 1

HCID 584167481-(4-(2-(3-aminopyridin-4-yl)ethoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of 3-tert-butyl-5-isocyanato-1-p-tolyl-1H-pyrazole (19) (530 mg, 2.076 mmol) in THF (2.0 mL) was added to a solution of 4-(2-(4-aminonaphthalen-1-yloxy)ethyl)pyridin-3-amine (18) (580 mg, 2.076 mmol) and DIPEA (1085 μl, 6.23 mmol) in THF (10 mL) and MeCN (1.0 mL) the reaction mixture stirred at RT overnight. The mixture was poured into brine (25 mL) and extracted with EtOAc (2×25 mL), dried, filtered and the solvent removed in vacuo. The product was pre-adsorbed onto hyflo (10 g), and purified by reverse phase column chromatography (40 g, C18 (from Silicycle), acetonitrile/water, 0 to 100%) and the product fractions concentrated in vacuo to give 1-(4-(2-(3-aminopyridin-4-yl)ethoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl) urea (Intermediate E) as an off white solid (410 mg, 36%). m/z 535 (M+H)+ (ES+).

Workup

  1. extractionextracted with EtOAc (2×25 mL)
  2. customdried
  3. filtrationfiltered
  4. customthe solvent removed in vacuo
  5. custompurified by reverse phase column chromatography (40 g
  6. concentrationC18 (from Silicycle), acetonitrile/water, 0 to 100%) and the product fractions concentrated in vacuo

Sources & evidence

ORD record
ord-ec865eefdf814adf98dd55c15db2dc67
Source dataset
uspto-grants-2013_12
Patent number
US08618140B2

Reaction notes

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