Phosgene → HCID 136105446, compound

HRID 1689995Notes

Reaction equation

HRID 1689995 reaction equation
C[O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[N:18]=[C:17]([N:19]2[CH2:24][CH2:23][CH:22]([OH:25])[CH2:21][CH2:20]2)[C:16]2[C:11](=[CH:12][C:13]([CH3:26])=[CH:14][CH:15]=2)[N:10]=1.[C:27](Cl)(Cl)=[O:28].[CH2:31]([NH2:35])[CH:32]([CH3:34])[CH3:33]>C1COCC1>[OH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[N:18]=[C:17]([N:19]2[CH2:24][CH2:23][CH:22]([O:25][C:27](=[O:28])[NH:35][CH2:31][CH:32]([CH3:34])[CH3:33])[CH2:21][CH2:20]2)[C:16]2[C:11](=[CH:12][C:13]([CH3:26])=[CH:14][CH:15]=2)[N:10]=1

Participants

5

Reactant 3

HCID 6371PhosgeneHCID 6558IsobutylamineHCID 66850173HCID 66850173, compound

Product 1

HCID 136105446HCID 136105446, compoundYield 66.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of 1-[2-(2-Methoxyphenyl)-7-methylquinazolin-4-yl]-piperidin-4-ol (100 mg, 0.30 mmol) and THF (500 μL) under N2, was added phosgene (317 μL, 0.60 mmol, 20% in toluene). The mixture was stirred at room temperature for 15 minutes. Isobutylamine (300 μL, 3.0 mmol) was added dropwise over a 2 minute period followed by stirring at room temperature for 1 hour. The mixture was evaporated to dryness and the obtained residue was purified via silica gel chromatography using 97% CH2Cl2/3% MeOH to obtain the desired carbamate intermediate as a clear oil (90 mg, 0.20 mmol). To a stirring solution of the carbamate intermediate (90 mg, 0.20 mmol) and CH2Cl2 (15 mL), under N2, at −78° C., was added BBr3 (0.60 mL, 0.60 mmol, 1.0 M in CH2Cl2) dropwise over a period of 2 minutes. The mixture was then allowed to warm to room temperature and was then heated at 50° C. for 15 minutes. The mixture was poured into a saturated aqueous NaHCO3 solution (80 mL) and the organic portion was evaporated to dryness. The residue was purified via HPLC to obtain the desired carbamate as a TFA salt (66 mg, 0.12 mmol, 39% yield). LC/MS (10-99%) M/Z 435.3 retention time 3.08 min.

Workup

  1. stirringby stirring at room temperature for 1 hour
  2. customThe mixture was evaporated to dryness
  3. customthe obtained residue was purified via silica gel chromatography

Sources & evidence

ORD record
ord-60a9a8f8cf6340aaa205719a1e028abc
Source dataset
uspto-grants-2012_04
Patent number
US08153642B2

Reaction notes

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