Ethyl chloroformate → HCID 136121330, compound

HRID 2062301Notes

Reaction equation

HRID 2062301 reaction equation
[NH2:1][CH2:2][C@@H:3]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]2[C:18]3[C:13](=[CH:14][C:15]([CH3:19])=[CH:16][CH:17]=3)[N:12]=[C:11]([C:20]3[C:25]([F:26])=[CH:24][CH:23]=[CH:22][C:21]=3[OH:27])[N:10]=2)[CH2:4]1.C(N(C(C)C)CC)(C)C.Cl[C:38]([O:40][CH2:41][CH3:42])=[O:39]>C1COCC1>[F:26][C:25]1[CH:24]=[CH:23][CH:22]=[C:21]([OH:27])[C:20]=1[C:11]1[N:10]=[C:9]([N:5]2[CH2:6][CH2:7][CH2:8][C@@H:3]([CH2:2][NH:1][C:38](=[O:39])[O:40][CH2:41][CH3:42])[CH2:4]2)[C:18]2[C:13](=[CH:14][C:15]([CH3:19])=[CH:16][CH:17]=2)[N:12]=1

Participants

5

Reactant 3

HCID 10928Ethyl chloroformateHCID 81531DiisopropylethylamineHCID 136121337HCID 136121337, compound

Product 1

HCID 136121330HCID 136121330, compoundYield 38.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

To a stirred solution of 2-(4-((S)-3-(aminomethyl)piperidin-1-yl)-7-methylquinazolin-2-yl)-3-fluorophenol (200 mg, 0.54 mmol) in 12 mL THF was added diisopropyl ethylamine (188 μL, 1.08 mmol) at room temperature. The mixture was cooled to—60° C., and a solution of ethyl chloroformate (52 μL, 0.54 mmol) in 0.6 mL THF was added dropwise. After allowing the reaction to warm to room temperature, the mixture was partitioned between H2O and CH2Cl2. The layers were separated, and the aqueous layer was extracted twice more with CH2Cl2. The organic layers were combined, dried over Na2SO4, filtered, and concentrated. Purification via silica gel chromatography using 0-10% EtOAc in 50:50 hexanes:CH2Cl2 gave ethyl ((S)-1-(2-(2-fluoro-6-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate (92 mg, 38%). LC/MS: m/z 439.5 (M+H)+ at 2.40 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. customthe reaction
  2. temperatureto warm to room temperature
  3. customthe mixture was partitioned between H2O and CH2Cl2
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted twice more with CH2Cl2
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-43de955bd09a4850be534710a9696e87
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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