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

HRID 2062263Notes

Reaction equation

HRID 2062263 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH3:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[OH:19])[N:3]=1.Cl.[NH:21]1[CH2:26][CH2:25][CH2:24][CH:23]([CH2:27][NH:28][C:29](=[O:38])[O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:22]1.C(N(CC)CC)C>C(Cl)Cl>[CH2:31]([O:30][C:29](=[O:38])[NH:28][CH2:27][CH:23]1[CH2:24][CH2:25][CH2:26][N:21]([C:2]2[C:11]3[C:6](=[CH:7][C:8]([CH3:12])=[CH:9][CH:10]=3)[N:5]=[C:4]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[OH:19])[N:3]=2)[CH2:22]1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 22350243HCID 22350243, compoundHCID 1361050322-(4-Chloro-7-methylquinazolin-2-yl)-phenol

Product 1

HCID 136121399Benzyl(1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamateYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

2-(4-Chloro-7-methylquinazolin-2-yl)phenol (1.5 g, 5.54 mmol) was suspended in anhydrous CH2Cl2 (15 mL) and cooled to 0° C. under an N2 atmosphere. A mixture of benzyl (piperidin-3-yl)methylcarbamate hydrochloride (1.73 g, 6.09 mmol) in CH2Cl2 (20 mL), and triethylamine (23 mL, 16.67 mmol) was added dropwise. The reaction mixture was allowed to warm to room temperature, and the reaction was complete after one hour. It was then partitioned between CH2Cl2/H2O, and separated, and the organic phase was dried over Na2SO4, filtered, and concentrated to an orange solid. Purification by silica gel chromatography using 98% CH2Cl2/2% EtOAc gave benzyl(1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate as a bright yellow solid (1.75 g, 66%). LC/MS: m/z 483.5 (M+H)+ at 2.81 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. additionwas added dropwise
  2. temperatureto warm to room temperature
  3. customIt was then partitioned between CH2Cl2/H2O
  4. customseparated
  5. dry with materialthe organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to an orange solid
  8. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-e68cb808c70c4d4092ef0528e041977f
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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