HCID 136201228, compound → HCID 136121356, compound

HRID 1693018Notes

Reaction equation

HRID 1693018 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]([NH:24]C(=O)OCC2C=CC=CC=2)[CH2:20]1>CO.[Pd]>[NH2:24][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 136201228HCID 136201228, compound

Product 1

HCID 136121356HCID 136121356, compoundYield 98%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

Under an N2 atmosphere, Pd/C (10% weight, 140 mg) was added to a solution of (R)-benzyl 1-(6-fluoro-2-(2-hydroxyphenyl)quinazolin-4-yl)pyrrolidin-3-ylcarbamate (1.37 g, 5.3 mmol) in MeOH (10 mL). After purging twice with N2 and evacuating the atmosphere in the flask containing the reaction mixture, the reaction was stirred under an H2 atmosphere overnight. The mixture was filtered through a pad of Celite, and the filtrate was concentrated under reduced pressure to obtain (R)-2-(4-(3-aminopyrrolidin-1-yl)-6-fluoroquinazolin-2-yl)phenol (940 mg, 98%). 1H NMR (400 MHz, CDCl3) δ 8.41 (m, 1H), 7.73 (m, 2H), 7.40 (m, 1H), 7.28 (m, 1H), 6.94 (m, 1H), 6.85 (m, 1H), 4.15 (m, 2H), 3.99 (m, 1H), 3.77 (m, 1H), 3.68 (m, 1H), 2.20 (m, 1H), 1.86 (m, 1H) ppm. LC/MS: m/z 325.3 (M+H)+ at 1.68 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. customAfter purging twice with N2
  2. customevacuating the atmosphere in the flask
  3. additioncontaining the reaction mixture
  4. filtrationThe mixture was filtered through a pad of Celite
  5. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-93774e44ff0a4b88982c544f4a3949a8
Source dataset
uspto-grants-2012_04
Patent number
US08158637B2

Reaction notes

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