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

HRID 2406197Notes

Reaction equation

HRID 2406197 reaction equation
[Cl:1][C:2]1[N:11]=[C:10]([N:12]2[CH2:16][CH2:15][C@@H:14]([NH2:17])[CH2:13]2)[C:9]2[C:4](=[CH:5][C:6]([CH3:18])=[CH:7][CH:8]=2)[N:3]=1.CCN(CC)CC.Cl[C:27]([O:29][CH2:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:28]>C1COCC1>[Cl:1][C:2]1[N:11]=[C:10]([N:12]2[CH2:16][CH2:15][C@@H:14]([NH:17][C:27](=[O:28])[O:29][CH2:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:13]2)[C:9]2[C:4](=[CH:5][C:6]([CH3:18])=[CH:7][CH:8]=2)[N:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 33521852,2-Dimethylpropyl carbonochloridateHCID 59758793(R)-1-(2-chloro-7-methylquinazolin-4-yl)pyrrolidin-3-amine

Product 1

HCID 59758785(R)-neopentyl 1-(2-chloro-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamateYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (R)-1-(2-chloro-7-methylquinazolin-4-yl)pyrrolidin-3-amine (100 mg, 0.38 mmol) in 2 mL of THF was cooled to −30° C. To it was added Et3N followed by the addition of neopentyl chloroformate (53 μL, 0.38 mmol) dropwise. The reaction was complete after 5 minutes. The reaction was quenched with water, the layers separated, and the aqueous layer was twice extracted with CH2Cl2. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification via silica gel chromatography using 0%-10% EtOAc in DCM gave (R)-neopentyl 1-(2-chloro-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate (100 mg, 70% yield). LC/MS: m/z 377.5 (M+H)+ at 2.90 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. customThe reaction was quenched with water
  2. customthe layers separated
  3. extractionthe aqueous layer was twice extracted with CH2Cl2
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-bca84e6ea2df4e0488190c5f0b39fba9
Source dataset
uspto-grants-2014_08
Patent number
US08809353B2

Reaction notes

Loading…