Propyl chloroformate → propyl((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-yl)methylcarbamate

HRID 2079435Notes

Reaction equation

HRID 2079435 reaction equation
[NH2:1][CH2:2][C@@H:3]1[CH2:7][CH2:6][N:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([CH3:18])=[CH:15][CH:16]=3)[N:11]=[C:10]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[OH:25])[N:9]=2)[CH2:4]1.C(N(CC)CC)C.Cl[C:34]([O:36][CH2:37][CH2:38][CH3:39])=[O:35]>C(Cl)Cl>[OH:25][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[C:10]1[N:9]=[C:8]([N:5]2[CH2:6][CH2:7][C@@H:3]([CH2:2][NH:1][C:34](=[O:35])[O:36][CH2:37][CH2:38][CH3:39])[CH2:4]2)[C:17]2[C:12](=[CH:13][C:14]([CH3:18])=[CH:15][CH:16]=2)[N:11]=1

Participants

5

Reactant 3

HCID 7998Propyl chloroformateHCID 8471TriethylamineHCID 1361213492-(4-((S)-3-(aminomethyl)pyrrolidin-1-yl)-7-methylquinazolin-2-yl)phenol

Product 1

HCID 136121353propyl((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-yl)methylcarbamateYield 62.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-30 °C

Procedure

A solution of 2-(4-((S)-3-(aminomethyl)pyrrolidin-1-yl)-7-methylquinazolin-2-yl)phenol (301 mg, 0.9 mmol) in CH2Cl2 (10 ml) was stirred under an N2 atmosphere. Triethylamine (0.25 mL, 1.8 mmol) was added, and the solution was cooled to −30° C. A 1 M propyl chloroformate solution (0.1 mL in 0.9 mL CH2Cl2, 0.9 mmol) was added, and the reaction mixture was allowed to warm to room temperature over a period of 30 minutes. After adding CH2Cl2 to the reaction mixture, it was washed 2 times with water, before it was dried over Na2SO4, filtered, and concentrated. Purification via silica gel chromatography using 0-20% EtOAc in CH2Cl2 gave propyl ((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-yl)methylcarbamate (236 mg, 62%). LC/MS: m/z 421 (M+H)+ at 2.54 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, DMSO-d6) δ 8.43 (dd, J=8.2, 1.8 Hz, 1H), 8.21 (d, J=8.7 Hz, 1H), 7.58 (s, 1H), 7.39-7.31 (m, 3H), 6.93-6.89 (m, 2H), 4.09-3.86 (m, 6H), 3.78-3.73 (m, 1H), 3.21-3.09 (m, 2H), 2.49 (s, 3H), 2.15-2.09 (m, 1H), 1.83-1.74 (m, 1H), 1.62-1.48 (m, 2H), 0.89-0.86 (m, 3H) ppm.

Workup

  1. temperatureto warm to room temperature over a period of 30 minutes
  2. washwas washed 2 times with water
  3. dry with materialbefore it was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-1c257499b1f14242a5f9ab6c2a3290c6
Source dataset
uspto-grants-2011_04
Patent number
US07928107B2

Reaction notes

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