Triphenylphosphine → (R)-tert-butyl 2-((S)-(4-chloro-3-fluorophenyl)(4-(2-(methylthio)pyrimidin-4-yl)-2-oxopyridin-1(2H)-yl)methyl)pyrrolidine-1-carboxylate

HRID 1774180노트

반응식

HRID 1774180 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8](O)[C@H:9]2[CH2:13][CH2:12][CH2:11][N:10]2[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[CH:4][C:3]=1[F:22].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.[CH3:56][S:57][C:58]1[N:63]=[C:62]([C:64]2[CH:69]=[CH:68][NH:67][C:66](=[O:70])[CH:65]=2)[CH:61]=[CH:60][N:59]=1>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([N:67]2[CH:68]=[CH:69][C:64]([C:62]3[CH:61]=[CH:60][N:59]=[C:58]([S:57][CH3:56])[N:63]=3)=[CH:65][C:66]2=[O:70])[C@H:9]2[CH2:13][CH2:12][CH2:11][N:10]2[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[CH:4][C:3]=1[F:22]

참가 물질

6

반응물 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 717270054-(2-(methylthio)pyrimidin-4-yl)pyridin-2(1H)-oneHCID 86696676(R)-tert-butyl 2-((R)-(4-chloro-3-fluorophenyl)(hydroxy)methyl)pyrrolidine-1-carboxylate

생성물 1

HCID 86696677(R)-tert-butyl 2-((S)-(4-chloro-3-fluorophenyl)(4-(2-(methylthio)pyrimidin-4-yl)-2-oxopyridin-1(2H)-yl)methyl)pyrrolidine-1-carboxylate

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

A solution of (R)-tert-butyl 2-((R)-(4-chloro-3-fluorophenyl)(hydroxy)methyl)pyrrolidine-1-carboxylate (0.662 g, 2.01 mmol) and triphenylphosphine (0.658 g, 2.51 mmol) in THF (40 mL) was placed in an ice bath, and diisopropyl azodicarboxylate (0.518 mL, 2.51 mmol) was added. The cold bath was removed after 10 minutes, and the reaction mixture was stirred at room temperature for 10 minutes. 4-(2-(Methylthio)pyrimidin-4-yl)pyridin-2(1H)-one (0.22 g, 1.00 mmol) was added, and the reaction was left at room temperature for 1 hour. The reaction mixture was concentrated, and the crude product was purified via column chromatography, eluting with hexanes/ethyl acetate (1:1) to give (R)-tert-butyl 2-((S)-(4-chloro-3-fluorophenyl)(4-(2-(methylthio)pyrimidin-4-yl)-2-oxopyridin-1(2H)-yl)methyl)pyrrolidine-1-carboxylate (contaminated with large amounts of PPh3O). m/z (APCI-pos) (M+1)-Boc=431.2, 433.2.

후처리

  1. customThe cold bath was removed after 10 minutes
  2. waitthe reaction was left at room temperature for 1 hour
  3. concentrationThe reaction mixture was concentrated
  4. customthe crude product was purified via column chromatography
  5. washeluting with hexanes/ethyl acetate (1:1)

출처 및 근거

ORD 기록
ord-55fbe9abdb2c41bd906933d8da4e08d7
출처 데이터셋
uspto-grants-2016_02
특허 번호
US09259470B2

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