Triphenylphosphine → tert-butyl 2-(2-{[6-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridin-3-yl]oxy}ethyl)pyrrolidine-1-carboxylate

HRID 1517282Notes

Reaction equation

HRID 1517282 reaction equation
[OH:1][CH2:2][CH2:3][CH:4]1[CH2:8][CH2:7][CH2:6][N:5]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.[CH3:47][N:48]1[CH:52]=[CH:51][C:50]([NH:53][C:54]2[C:63]3[C:58](=[CH:59][CH:60]=[C:61]([O:64][C:65]4[N:70]=[CH:69][C:68](O)=[CH:67][CH:66]=4)[CH:62]=3)[N:57]=[CH:56][N:55]=2)=[N:49]1>C(Cl)(Cl)Cl.O1CCCC1>[CH3:47][N:48]1[CH:52]=[CH:51][C:50]([NH:53][C:54]2[C:63]3[C:58](=[CH:59][CH:60]=[C:61]([O:64][C:65]4[N:70]=[CH:69][C:68]([O:1][CH2:2][CH2:3][CH:4]5[CH2:8][CH2:7][CH2:6][N:5]5[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[CH:67][CH:66]=4)[CH:62]=3)[N:57]=[CH:56][N:55]=2)=[N:49]1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 13425759tert-Butyl 2-(2-hydroxyethyl)pyrrolidine-1-carboxylateHCID 684298776-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridin-3-ol

Product 1

HCID 68427619tert-butyl 2-(2-{[6-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridin-3-yl]oxy}ethyl)pyrrolidine-1-carboxylateYield 90.9%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Procedure

Tert-butyl 2-(2-hydroxyethyl)pyrrolidine-1-carboxylate (260 mg, 1.2 mmol), triphenyl phosphine (310 mg, 1.2 mmol) and diethyl azodicarboxylate (0.19 mmol, 1.2 mmol) were added to a tetrahydrofuran solution (6 ml) of 6-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridin-3-ol (200 mg, 0.60 mmol) obtained in Example 6, and the reaction solution was stirred at room temperature for 30 minutes. The reaction solution was diluted with chloroform, the organic layer was washed with water and saturated saline water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform:methanol=96:4) and amine-type silica gel column chromatography (hexane:ethyl acetate=50:50) to obtain tert-butyl 2-(2-{[6-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridin-3-yl]oxy}ethyl)pyrrolidine-1-carboxylate (290 mg, yield: 90.5%) as a pale yellow amorphous solid.

Workup

  1. washthe organic layer was washed with water and saturated saline water
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe obtained residue was purified by silica gel column chromatography (chloroform:methanol=96:4) and amine-type silica gel column chromatography (hexane:ethyl acetate=50:50)

Sources & evidence

ORD record
ord-1f6743b4e1cb49d580398b91567a85cb
Source dataset
uspto-grants-2012_07
Patent number
US08232284B2

Reaction notes

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