Triethylamine → (R)-tert-butyl 1-(2-chloro-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate

HRID 1693036Notes

Reaction equation

HRID 1693036 reaction equation
[Cl:1][C:2]1[N:11]=[C:10](Cl)[C:9]2[C:4](=[CH:5][C:6]([CH3:13])=[CH:7][CH:8]=2)[N:3]=1.[NH:14]1[CH2:18][CH2:17][C@@H:16]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:15]1.CCN(CC)CC>ClCCl>[Cl:1][C:2]1[N:11]=[C:10]([N:14]2[CH2:18][CH2:17][C@@H:16]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:24])([CH3:23])[CH3:25])[CH2:15]2)[C:9]2[C:4](=[CH:5][C:6]([CH3:13])=[CH:7][CH:8]=2)[N:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1514397(3R)-(+)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 219419832,4-Dichloro-7-methylquinazoline

Product 1

HCID 59758791(R)-tert-butyl 1-(2-chloro-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamateYield 83%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2,4-Dichloro-7-methylquinazoline (2.0 g, 9.4 mmol) was suspended in 40 mL of dichloromethane under an N2 atmosphere and cooled to 0° C. (R)-tert-Butyl pyrrolidin-3-ylcarbamate (1.75 g, 9.4 mmol) was dissolved in a solution of 10 mL of dichloromethane and Et3N (2.62 mL, 18.8 mmol) and added dropwise to the above reaction mixture. The reaction was warmed to RT and stirred for 16 hours. The reaction was quenched with water, extracted with DCM, dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification via silica gel chromatography using 0%-10% EtOAc in DCM gave (R)-tert-butyl 1-(2-chloro-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate (2.82 g, 83% yield). LC/MS: m/z 363.1 (M+H)+ at 3.26 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. additionadded dropwise to the above reaction mixture
  2. customThe reaction was quenched with water
  3. extractionextracted with DCM
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-e8dba6b2902a4c1fb953742afe3a3e89
Source dataset
uspto-grants-2012_04
Patent number
US08158637B2

Reaction notes

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