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

HRID 81642Notes

Reaction equation

HRID 81642 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.[CH3:45][N:46]1[CH:50]=[CH:49][C:48]([NH:51][C:52]2[C:61]3[C:56](=[CH:57][CH:58]=[C:59]([O:62][C:63]4[N:68]=[CH:67][C:66](O)=[CH:65][CH:64]=4)[CH:60]=3)[N:55]=[CH:54][N:53]=2)=[N:47]1>C(Cl)(Cl)Cl.O1CCCC1>[CH3:45][N:46]1[CH:50]=[CH:49][C:48]([NH:51][C:52]2[C:61]3[C:56](=[CH:57][CH:58]=[C:59]([O:62][C:63]4[N:68]=[CH:67][C:66]([O:1][CH2:2][CH:3]5[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4]5)=[CH:65][CH:64]=4)[CH:60]=3)[N:55]=[CH:54][N:53]=2)=[N:47]1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 10583745tert-Butyl 3-(hydroxymethyl)azetidine-1-carboxylateHCID 684298776-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridin-3-ol

Product 1

HCID 68430704tert-butyl 3-({[6-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridin-3-yl]oxy}methyl)azetidine-1-carboxylateYield 90%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Procedure

Tert-butyl 3-(hydroxymethyl)azetidine-1-carboxylate (110 mg, 0.60 mmol), triphenyl phosphine (160 mg, 0.60 mmol) and diethyl azodicarboxylate (0.095 mmol, 0.60 mmol) were added to a tetrahydrofuran solution (3 ml) of 6-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridin-3-ol (100 mg, 0.30 mmol) obtained in Example 6-3), 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 3-({[6-({4-[(1-methyl-1H-pyrazol-3-yl)amino]quinazolin-6-yl}oxy)pyridin-3-yl]oxy}methyl)azetidine-1-carboxylate (136 mg, yield: 90%) 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-f47300c70fd44c9ab7bcfce5d08bfcfb
Source dataset
uspto-grants-2014_09
Patent number
US08846700B2

Reaction notes

Loading…