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

HRID 1693040Notes

Reaction equation

HRID 1693040 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-611ad9c1683740359e39d2538b56a866
Source dataset
uspto-grants-2012_04
Patent number
US08158637B2

Reaction notes

Loading…