Diisopropylethylamine → [(R)-2-(3-cyano-azetidin-1-yl)-1-methoxymethyl-2-oxo-ethyl]-carbamic acid tert-butyl ester

HRID 246171노트

반응식

HRID 246171 반응식
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:13][O:14][CH3:15])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[NH:17]1[CH2:20][CH:19]([C:21]#[N:22])[CH2:18]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([CH2:13][O:14][CH3:15])[C:10]([N:17]1[CH2:20][CH:19]([C:21]#[N:22])[CH2:18]1)=[O:12])([CH3:2])([CH3:3])[CH3:4]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27281801(2R)-2-{[(tert-butoxy)carbonyl]amino}-3-methoxypropanoic acidHCID 45072465Azetidine-3-carbonitrile hydrochloride

생성물 1

HCID 71280690[(R)-2-(3-cyano-azetidin-1-yl)-1-methoxymethyl-2-oxo-ethyl]-carbamic acid tert-butyl ester수율 47%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A 25 mL round-bottomed flask was charged with (R)-2-tert-butoxycarbonylamino-3-methoxy-propionic acid (0.475 g, 2.17 mmol), azetidine-3-carbonitrile hydrochloride (314 mg, 2.65 mmol) and HATU (832 mg, 2.19 mmol). Then added DMF (3.6 mL) followed by N,N-diisopropylethylamine (1.5 mL, 8.67 mmol). The reaction mixture was stirred at room temperature overnight then quenched with water and extracted with EtOAc (30 mL). The organic layer was washed once with saturated NaHCO3 and water. The combined aqueous layers were back extracted with EtOAc (25 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography over SiO2 with EtOAc/heptane (gradient: 0-100% EtOAc) to afford 288 mg (47%) of [(R)-2-(3-cyano-azetidin-1-yl)-1-methoxymethyl-2-oxo-ethyl]-carbamic acid tert-butyl ester as a viscous colorless oil.

후처리

  1. customthen quenched with water
  2. extractionextracted with EtOAc (30 mL)
  3. washThe organic layer was washed once with saturated NaHCO3 and water
  4. extractionThe combined aqueous layers were back extracted with EtOAc (25 mL)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography over SiO2 with EtOAc/heptane (gradient: 0-100% EtOAc)

출처 및 근거

ORD 기록
ord-55bd59b9ea3a4c1e817aa341a77d7064
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

반응 노트

불러오는 중…