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

HRID 2062274

Reaction equation

HRID 2062274 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.Cl[C:28]([O:30][C@H:31]1[CH2:35][CH2:34][O:33][CH2:32]1)=[O:29].C(N(CC)CC)C>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:28](=[O:29])[O:30][C@H:31]3[CH2:35][CH2:34][O:33][CH2:32]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 1361213552-(4-((S)-3-(Aminomethyl)piperidin-1-yl)-7-methylquinazolin-2-yl)phenol

Product 1

HCID 136121431(S)-Tetrahydrofuran-3-yl((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamateYield 64.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(4-((S)-3-(aminomethyl)piperidin-1-yl)-7-methylquinazolin-2-yl)phenol (175 mg, 0.5 mmol) in DMF at 0° C. were added (S)-tetrahydrofuran-3-yl chloroformate (75 mg, 0.5 mmol) and triethylamine (137 μL, 1.0 mmol) simultaneously. Ten to fifteen minutes after addition, the reaction was complete, and it was quenched with water and extracted with CH2Cl2. The combined organic layers were dried over MgSO4, filtered, and concentrated. Purification via silica gel chromatography using 98% CH2Cl2/2% MeOH gave (S)-tetrahydrofuran-3-yl ((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate (150 mg, 54%). LC/MS: m/z 463.5 (M+H)+ at 2.37 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. additionTen to fifteen minutes after addition
  2. customit was quenched with water
  3. extractionextracted 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-99782cac32f44e43ba4412c8765d1231
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Linked notes

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