Triethylamine → (S)-tetrahydrofuran-3-yl ((R)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate

HRID 2079365Notes

Reaction equation

HRID 2079365 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[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[OH:26])[N:10]=2)[CH2:4]1.C(N(CC)CC)C.Cl[C:35]([O:37][C@H:38]1[CH2:42][CH2:41][O:40][CH2:39]1)=[O:36]>CN(C=O)C>[OH:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][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:35](=[O:36])[O:37][C@H:38]3[CH2:42][CH2:41][O:40][CH2:39]3)[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 8471TriethylamineHCID 22876378(3S)-oxolan-3-yl carbonochloridateHCID 1361214762-(4-((R)-3-(Aminomethyl)piperidin-1-yl)-7-methylquinazolin-2-yl)phenol

Product 1

HCID 136121578(S)-tetrahydrofuran-3-yl ((R)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2-(4-((R)-3-(aminomethyl)piperidin-1-yl)-7-methylquinazolin-2-yl)phenol (200 mg, 0.57 mmol) in DMF under an N2 atmosphere at 0° C. was added triethylamine (115 mg, 1.14 mmol) followed by the dropwise addition of (S)-tetrahydrofuran-3-yl chloroformate (86 mg, 0.57 mmol). The reaction was allowed to warm to room temperature and was stirred for 2 h. The mixture was partitioned between H2O and CH2Cl2 and separated, and the aqueous layer was extracted twice with CH2Cl2. The organic layers were combined, dried over Na2SO4, filtered, and concentrated. Purification via silica gel chromatography using 4:1 CH2Cl2:EtOAc afforded (S)-tetrahydrofuran-3-yl ((R)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate. LC/MS: m/z 463.5 (M+H)+ at 2.34 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. customThe mixture was partitioned between H2O and CH2Cl2
  2. customseparated
  3. extractionthe aqueous layer was extracted twice with CH2Cl2
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-bae9f556fc334df7ba26bd8264005e87
Source dataset
uspto-grants-2011_04
Patent number
US07928107B2

Reaction notes

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