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

HRID 2406195Notes

Reaction equation

HRID 2406195 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][CH:31]([CH3:33])[CH3:32])=[O:28]>ClCCl>[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][CH:31]([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 62365Isobutyl chloroformateHCID 59758793(R)-1-(2-chloro-7-methylquinazolin-4-yl)pyrrolidin-3-amine

Product 1

HCID 59758788(R)-isobutyl 1-(2-chloro-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamateYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (R)-1-(2-chloro-7-methylquinazolin-4-yl)pyrrolidin-3-amine (100 mg, 0.38 mmol) in 2 mL of dichloromethane was cooled to −30° C. To it was added Et3N followed by the addition of isobutyl chloroformate 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. Purification via silica gel chromatography using 0%-10% EtOAc in DCM gave (R)-isobutyl 1-(2-chloro-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate (90 mg, 66% yield). LC/MS: m/z 363.3 (M+H)+ at 2.74 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
  7. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-7825c5643c514c13a37467fdb17c3dca
Source dataset
uspto-grants-2014_08
Patent number
US08809353B2

Reaction notes

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