Triphenylphosphine → (R)-4-((R)-1-((5-bromo-1-cyclopropyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

HRID 2209039노트

반응식

HRID 2209039 반응식
[Br:1][C:2]1[CH:13]=[C:12]([OH:14])[C:5]2[N:6]([CH:9]3[CH2:11][CH2:10]3)[CH:7]=[N:8][C:4]=2[CH:3]=1.O[C@H:16]([C@H:18]1[CH2:22][N:21]([C@@H:23]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[CH3:24])[C:20](=[O:33])[CH2:19]1)[CH3:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[Br:1][C:2]1[CH:13]=[C:12]([O:14][C@@H:16]([C@H:18]2[CH2:22][N:21]([C@@H:23]([C:25]3[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=3)[CH3:24])[C:20](=[O:33])[CH2:19]2)[CH3:17])[C:5]2[N:6]([CH:9]3[CH2:11][CH2:10]3)[CH:7]=[N:8][C:4]=2[CH:3]=1

참가 물질

6

반응물 4

HCID 11776Triphenylphosphine2회HCID 220568ethyl N-ethoxycarbonyliminocarbamate2회HCID 71238294(4R)-4-[(1S)-1-hydroxyethyl]-1-[(1R)-1-(4-methoxyphenyl)ethyl]pyrrolidin-2-one2회HCID 1178436505-Bromo-1-cyclopropyl-1H-benzo[d]imidazol-7-ol

생성물 1

HCID 117844014(R)-4-((R)-1-((5-bromo-1-cyclopropyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

5-bromo-1-cyclopropyl-1H-benzo[d]imidazol-7-ol 2.73 (1.4 g, 5.53 mmol), (R)-4-((S)-1-hydroxyethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin- 2-one 1.05 (2.04 g, 7.75 mmol), and triphenylphosphine (2.04 g, 7.78 mmol) were taken up in THF (30 mL). Diethyl azodicarboxylate (1.2 ml, 7.65 mmol) was added dropwise over 1 min, and the resulting stirred solution was heated to 40 C. After 1 h, add additional portions of intermediate 1.05 (0.27 g, 1.02 mmol), triphenylphosphine (0.27 g, 1.02 mmol), and diethyl azodicarboxylate (0.15 ml, 0.96 mmol) were added. The mixture was stirred an additional 1.5 h and was then concentrated directly onto silica gel. Purification by silica gel chromatography (20-100% acetone:hexanes) provided (R)-4-((R)-1-((5-bromo-1-cyclopropyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one (2.74). LCMS-ESI+ (m/z): [M+H]+ calcd for C25H29BrN3O3: 498.14; found: 498.37.

후처리

  1. temperaturewas heated to 40 C
  2. additionwere added
  3. stirringThe mixture was stirred an additional 1.5 h
  4. concentrationwas then concentrated directly onto silica gel
  5. customPurification by silica gel chromatography (20-100% acetone:hexanes)

출처 및 근거

ORD 기록
ord-d4bf033951e94bc0948331d4ec37fb8b
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09376441B2

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