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

HRID 2062344Notes

Reaction equation

HRID 2062344 reaction equation
C(N(CC)CC)C.[CH2:8]([O:15][C:16](=[O:24])[NH:17][CH2:18][C@@H:19]1[CH2:23][CH2:22][NH:21][CH2:20]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.Cl[C:26]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([F:36])[CH:34]=2)[N:29]=[C:28]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=2[OH:43])[N:27]=1>C(Cl)Cl>[CH2:8]([O:15][C:16](=[O:24])[NH:17][CH2:18][C@@H:19]1[CH2:23][CH2:22][N:21]([C:26]2[C:35]3[C:30](=[CH:31][CH:32]=[C:33]([F:36])[CH:34]=3)[N:29]=[C:28]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=3[OH:43])[N:27]=2)[CH2:20]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 45072660benzyl ((R)-pyrrolidin-3-yl)methylcarbamateHCID 1361214352-(4-Chloro-6-fluoroquinazolin-2-yl)phenol

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of triethylamine (507 μL, 3.64 mmol) and benzyl((R)-pyrrolidin-3-yl)methylcarbamate (0.47 g, 2 mmol) in CH2Cl2 was added dropwise to a solution of 2-(4-chloro-6-fluoroquinazolin-2-yl)phenol (0.5 g, 1.82 mmol) in CH2Cl2 (20 mL). The reaction was stirred at room temperature for 3 h. After quenching the reaction with water, the aqueous phase was extracted twice with CH2Cl2. The combined organic layers were dried over MgSO4, filtered, and concentrated. Purification via silica gel chromatography using 5-10% EtOAc in CH2Cl2 yielded benzyl((S)-1-(6-fluoro-2-(2-hydroxyphenyl)quinazolin-4-yl)pyrrolidin-3-yl)methylcarbamate. LC/MS: m/z 473.1 (M+H)+ at 2.91 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. customAfter quenching
  2. customthe reaction with water
  3. extractionthe aqueous phase was extracted twice with CH2Cl2
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-e4cfa81bfad5412fbea090d2219a23ef
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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