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 2069035Notes

Reaction equation

HRID 2069035 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 (28) (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 (27) (580 mg, 2.076 mmol) and DIPEA (1085 μL, 6.23 mmol) in THF (10 mL) and MeCN (1.0 mL) and 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 the title compound (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-8b758fe56ffe4db6a53dee85f4b4e5f7
Source dataset
uspto-grants-2012_10
Patent number
US08299073B2

Reaction notes

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