Dichloromethane → (7R,7aS)-2-Chloro-4-(7-hydroxy-7a-methyl-1,3-dioxotetrahydropyrrolo[1,2-c]imidazol-2-yl)-3-methylbenzonitrile

HRID 751088노트

반응식

HRID 751088 반응식
CO[C:3]([C@:5]1([CH3:18])[C@H:9]([OH:10])[CH2:8][CH2:7][N:6]1[C:11]([O:13]C(C)(C)C)=O)=[O:4].CC[N:21](C(C)C)C(C)C.Cl[C:29]1[C:30](C)=[C:31]([CH2:35][C:36]([NH2:38])=O)C=[CH:33][CH:34]=1.[CH2:40]([Cl:42])Cl>>[Cl:42][C:40]1[C:34]([CH3:33])=[C:29]([N:21]2[C:3](=[O:4])[C@:5]3([CH3:18])[C@H:9]([OH:10])[CH2:8][CH2:7][N:6]3[C:11]2=[O:13])[CH:30]=[CH:31][C:35]=1[C:36]#[N:38]

참가 물질

5

반응물 4

HCID 6344DichloromethaneHCID 81531DiisopropylethylamineHCID 59754263(2S,3R)-3-Hydroxy-2-methylpyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl esterHCID 684549373-Chloro-2-methylphenylacetamide

생성물 1

HCID 59754251(7R,7aS)-2-Chloro-4-(7-hydroxy-7a-methyl-1,3-dioxotetrahydropyrrolo[1,2-c]imidazol-2-yl)-3-methylbenzonitrile

실험 절차

To a solution of (2S,3R)-3-hydroxy-2-methyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (25A) (87 mg, 0.32 mmol) in CH2Cl2 (1.3 mL) at 0° C. was added Hunig's base (111 mL, 0.64 mmol). After stirring for 15 min, 2-chloro-4-isocyanato-3-methylbenzonitrile (23A) was added, and after an additional 10 min, the ice bath was removed. The reaction was stirred for 2 h and then diluted with water. The layers were separated and the organic layer was washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure. The resulting solid was purified using preparative HPLC (Luna C-18, 21.2×100 mm, eluting with 40-100% solvent B (A=90% H2O—10% MeOH and B=10% H2O—90% MeOH) over 15 min; Flow rate at 20 mL/min; UV detection at 220 nm) to provide the title compound (67 mg) as a white film; LC/MS m/z 661 [2M+23]+.

후처리

  1. waitafter an additional 10 min
  2. customthe ice bath was removed
  3. stirringThe reaction was stirred for 2 h
  4. additiondiluted with water
  5. customThe layers were separated
  6. washthe organic layer was washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting solid was purified
  11. washeluting with 40-100% solvent B (A=90% H2O—10% MeOH and B=10% H2O—90% MeOH) over 15 min

출처 및 근거

ORD 기록
ord-0b74f585dee24eec907c8cac2e8ac55b
출처 데이터셋
uspto-grants-2008_07
특허 번호
US07405234B2

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