Diisopropylethylamine → 3-(2-Chloropyrimidin-5-yl)-5,5-dimethyl-imidazolidine-2,4-dione

HRID 1484643노트

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HRID 1484643 반응식
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[Cl:13][C:14]1[N:19]=[CH:18][C:17]([NH2:20])=[CH:16][N:15]=1.CCN(C(C)C)C(C)C.Cl.C[O:32][C:33](=O)[C:34]([CH3:37])([CH3:36])[NH2:35]>C(OCC)(=O)C.CN(C1C=CN=CC=1)C.C(OCC)(=O)C.ClCCl>[Cl:13][C:14]1[N:19]=[CH:18][C:17]([N:20]2[C:33](=[O:32])[C:34]([CH3:37])([CH3:36])[NH:35][C:5]2=[O:11])=[CH:16][N:15]=1

참가 물질

8

반응물 4

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 122159932-Chloropyrimidin-5-amineHCID 13258034Methyl 2-aminoisobutyrate hydrochloride

생성물 1

HCID 866984523-(2-Chloropyrimidin-5-yl)-5,5-dimethyl-imidazolidine-2,4-dione

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 8857Ethyl Acetate용매3회HCID 21226138Dichloromethane ethylacetate용매

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온도
0 °C

실험 절차

To a solution of triphosgene (1.38 g, 4.65 mmol) in Ethyl acetate (20 ml) at 0° C. a solution of 2-chloro-5-aminopyrimidine (1 g, 7.75 mmol)/DIPEA (8 ml, 4.65 mmol) in ethyl acetate (40 ml) was slowly added (20 minutes) and the reaction mixture was stirred for 15 minutes at the same temperature. Maintaining the reaction mixture at 0° C., vacuum was applied (10 minutes) for removing the excess of phosgene. A solution of DMAP (0.945 g, 7.75 mmol) in ethyl acetate/dichloromethane 1:1 (8 ml) was added and the reaction mixture was stirred for 5 minutes at the same temperature. 2,2-Dimethylglycine methyl ester hydrochloride (2.37 g, 15.5 mmol) in ethyl acetate (30 ml) was slowly added (15 minutes) at 0° C. and the reaction mixture was stirred for 30 minutes at the same temperature. The reaction was quenched with aqueous buffer (pH3) while the pH was allowed to reach ˜5-6 and two phases were separated. The organic layer was washed with aqueous buffer (pH3) (2×20 ml) and then brine (20 ml), dried (Na2SO4), filtered and evaporated affording the urea intermediate as orange foam.

후처리

  1. custom(10 minutes)
  2. customfor removing the excess of phosgene
  3. stirringthe reaction mixture was stirred for 5 minutes at the same temperature
  4. stirringthe reaction mixture was stirred for 30 minutes at the same temperature
  5. customThe reaction was quenched with aqueous buffer (pH3) while the pH
  6. customwere separated
  7. washThe organic layer was washed with aqueous buffer (pH3) (2×20 ml)
  8. dry with materialbrine (20 ml), dried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated

출처 및 근거

ORD 기록
ord-2cf15385a09848028bfbfb1813015550
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09422272B2

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