Diisopropylethylamine → (R)-ethyl 5-(4-(tert-butyldimethylsilyloxy)-2-(5-fluoro-2-methoxyphenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate

HRID 1426897노트

반응식

HRID 1426897 반응식
O[C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[CH:9][C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:4]2[N:3]=1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.FC(F)(F)C(O)=O.[Si:50]([O:57][CH:58]1[CH2:62][NH:61][C@@H:60]([C:63]2[CH:68]=[C:67]([F:69])[CH:66]=[CH:65][C:64]=2[O:70][CH3:71])[CH2:59]1)([C:53]([CH3:56])([CH3:55])[CH3:54])([CH3:52])[CH3:51].C(N(CC)C(C)C)(C)C>CN(C=O)C.C(Cl)Cl.CCOC(C)=O>[Si:50]([O:57][CH:58]1[CH2:62][N:61]([C:2]2[CH:7]=[CH:6][N:5]3[N:8]=[CH:9][C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:4]3[N:3]=2)[C@@H:60]([C:63]2[CH:68]=[C:67]([F:69])[CH:66]=[CH:65][C:64]=2[O:70][CH3:71])[CH2:59]1)([C:53]([CH3:56])([CH3:55])[CH3:54])([CH3:51])[CH3:52]

참가 물질

8

반응물 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 67470685(R)-4-(tert-butyldimethylsilyloxy)-2-(5-fluoro-2-methoxyphenyl)pyrrolidine 2,2,2-trifluoroacetateHCID 178469952HCID 178469952, 화합물

생성물 1

HCID 86691711(R)-ethyl 5-(4-(tert-butyldimethylsilyloxy)-2-(5-fluoro-2-methoxyphenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate수율 19.6%

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

To a suspension of ethyl 5-hydroxypyrazolo[1,5-a]pyrimidine-3-carboxylate (0.100 g, 0.483 mmol) and BOP reagent (0.320 g, 0.724 mmol) in DMF (1 mL) at 0° C. was added a solution of (R)-4-(tert-butyldimethylsilyloxy)-2-(5-fluoro-2-methoxyphenyl)pyrrolidine 2,2,2-trifluoroacetate (Preparation C, 0.167 g, 0.483 mmol) in CH2Cl2 (1 mL) and N,N-diisopropylethylamine (0.420 mL, 2.41 mmol) sequentially. The resulting mixture was warmed to ambient temperature and stirred for 18 hours. The reaction mixture was diluted with EtOAc (10 mL), and washed with saturated aqueous NaHCO3 and brine. The brine phase was back-extracted with EtOAc (3×). The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude material that was purified by silica column chromatography, eluting with 0-50% EtOAc/Hexanes to afford (R)-ethyl 5-(4-(tert-butyldimethylsilyloxy)-2-(5-fluoro-2-methoxyphenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (as a mixture of cis and trans isomers) (0.0487 g, 19.6% yield). LC/MS (ES+APCI) m/z=515.2 (M+H).

후처리

  1. washwashed with saturated aqueous NaHCO3 and brine
  2. extractionThe brine phase was back-extracted with EtOAc (3×)
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto give the crude material that
  7. customwas purified by silica column chromatography
  8. washeluting with 0-50% EtOAc/Hexanes

출처 및 근거

ORD 기록
ord-92378169516a4e759a850ae3037cf515
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08933084B2

반응 노트

불러오는 중…