benzyl((S)-1-(6-fluoro-2-(2-hydroxyphenyl)quinazolin-4-yl)pyrrolidin-3-yl)methylcarbamate → 2-(4-((S)-3-(aminomethyl)pyrrolidin-1-yl)-6-fluoroquinazolin-2-yl)phenol

HRID 2079428Notes

Reaction equation

HRID 2079428 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[OH:18])[N:6]=[C:5]2[N:19]1[CH2:23][CH2:22][C@@H:21]([CH2:24][NH:25]C(=O)OCC2C=CC=CC=2)[CH2:20]1>[Pd].CO>[NH2:25][CH2:24][C@@H:21]1[CH2:22][CH2:23][N:19]([C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([F:1])[CH:3]=3)[N:8]=[C:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[OH:18])[N:6]=2)[CH2:20]1

Participants

4

Reactant 1

HCID 136121333benzyl((S)-1-(6-fluoro-2-(2-hydroxyphenyl)quinazolin-4-yl)pyrrolidin-3-yl)methylcarbamate

Product 1

HCID 1361214102-(4-((S)-3-(aminomethyl)pyrrolidin-1-yl)-6-fluoroquinazolin-2-yl)phenolYield 83.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

Under an N2 atmosphere, a mixture of benzyl ((S)-1-(6-fluoro-2-(2-hydroxyphenyl)quinazolin-4-yl)pyrrolidin-3-yl)methylcarbamate (0.770 g, 1.6 mmol) and MeOH (5 mL) was added to Pd/C (77 mg, 10% weight Pd on carbon) weighed into a 100 mL flask. After the atmosphere in the flask was evacuated and purged with N2 three times, the reaction mixture was vigorously stirred under an H2 atmosphere at ambient pressure overnight and then filtered through a pad of Celite, concentrated, and dried to obtain 2-(4-((S)-3-(aminomethyl)pyrrolidin-1-yl)-6-fluoroquinazolin-2-yl)phenol (0.45 g, 81%). LC/MS: m/z 459.5 (M+H)+ at 2.81 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. customweighed into a 100 mL flask
  2. customAfter the atmosphere in the flask was evacuated
  3. custompurged with N2 three times
  4. filtrationfiltered through a pad of Celite
  5. concentrationconcentrated
  6. customdried

Sources & evidence

ORD record
ord-a5b40871593a4a17ab9ff1fc9642af75
Source dataset
uspto-grants-2011_04
Patent number
US07928107B2

Reaction notes

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