Triethylamine → HCID 136121380, compound

HRID 2406180Notes

Reaction equation

HRID 2406180 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.[C:20]([O:24][C:25](=[O:32])[NH:26][C@H:27]1[CH2:31][CH2:30][NH:29][CH2:28]1)([CH3:23])([CH3:22])[CH3:21].C(N(CC)CC)C>C(Cl)Cl.O>[C:20]([O:24][C:25](=[O:32])[NH:26][C@H:27]1[CH2:31][CH2:30][N:29]([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)[CH2:28]1)([CH3:23])([CH3:21])[CH3:22]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 1514396(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 1361050322-(4-Chloro-7-methylquinazolin-2-yl)-phenol

Product 1

HCID 136121380HCID 136121380, compoundYield 76.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

To 2-(4-chloro-7-methyl-quinazolin-2-yl)-phenol (300 mg, 1.1 mmol) in 1.8 mL of CH2Cl2 at 0° C. was added (S)-pyrrolidin-3-yl-carbamic acid tert-butyl ester (246 mg, 1.32 mmol) in 1.8 mL of CH2Cl2, followed by triethylamine (184 μL, 1.32 mmol). The reaction mixture was stirred from 0° C. to room temperature over 16 h. The reaction mixture was diluted with 10 mL of CH2Cl2 and 10 mL of water, and the organic layer was separated and dried over Na2SO4. The solvent was removed under reduced pressure, and the residue was purified via silica gel chromatography using 10-100% EtOAc in hexanes to give of (S)-{1-[2-(2-hydroxy-phenyl)-7-methyl-quinazolin-4-yl]-pyrrolidin-3-yl}-carbamic acid tert-butyl ester (352 mg, 70%). LC/MS: m/z 421 (M+H)+ at 2.84 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. customthe organic layer was separated
  2. dry with materialdried over Na2SO4
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was purified via silica gel chromatography

Sources & evidence

ORD record
ord-7d6d6f2cba7445258006e1b30c6133aa
Source dataset
uspto-grants-2014_08
Patent number
US08809353B2

Reaction notes

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