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

HRID 1426986노트

반응식

HRID 1426986 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.Cl.[F:44][C:45]1[CH:46]=[CH:47][C:48]([O:57][CH3:58])=[C:49]([CH:51]2[NH:55][CH2:54][C@H:53]([OH:56])[CH2:52]2)[CH:50]=1.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl.CCOC(C)=O>[F:44][C:45]1[CH:46]=[CH:47][C:48]([O:57][CH3:58])=[C:49]([C@H:51]2[CH2:52][CH:53]([OH:56])[CH2:54][N:55]2[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)[CH:50]=1

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 67470690(R)-5-(5-fluoro-2-methoxyphenyl)pyrrolidin-3-ol hydrochlorideHCID 178469952HCID 178469952, 화합물

생성물 1

HCID 86691712(R)-ethyl 5-(2-(5-fluoro-2-methoxyphenyl)-4-hydroxypyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate수율 77.6%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 22350042dichloromethane N,N-dimethylformamide용매

실험 절차

To a suspension of ethyl 5-hydroxypyrazolo[1,5-a]pyrimidine-3-carboxylate (0.541 g, 2.61 mmol) and BOP reagent (1.57 g, 3.56 mmol) in DMF/CH2Cl2 (3 mL/3 mL) at 0° C. was added (R)-5-(5-fluoro-2-methoxyphenyl)pyrrolidin-3-ol hydrochloride (0.588 g, 2.37 mmol) followed by DIEA (1.66 mL, 9.50 mmol). The resulting mixture was warmed to ambient temperature and stirred for 18 hours. The reaction mixture was concentrated under reduced pressure to give the crude material that was diluted again with EtOAc (30 mL). The organic layer was washed with saturated aqueous NaHCO3 followed by brine, dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude material that was purified by silica gel flash column chromatography, eluting with CH2Cl2 to 5% MeOH in CH2Cl2 to afford (R)-ethyl 5-(2-(5-fluoro-2-methoxyphenyl)-4-hydroxypyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (0.735 g, 1.84 mmol, 77.3% yield). LC/MS (ES+APCI) m/z=401.1 (M+H).

후처리

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto give the crude material that
  3. washThe organic layer was washed with saturated aqueous NaHCO3
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give the crude material that
  8. customwas purified by silica gel flash column chromatography
  9. washeluting with CH2Cl2 to 5% MeOH in CH2Cl2

출처 및 근거

ORD 기록
ord-67ee4369e7dc49d4a6b90300d5f30e8f
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08933084B2

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