Acetic Acid → (S)-4-(3-((S)-6-(bis((1-(2-tert-butoxy-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)-1-tert-butoxy-1-oxohexan-2-yl)ureido)-5-tert-butoxy-5-oxopentanoic acid

HRID 1509785

반응식

HRID 1509785 반응식
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][C@H:6]([NH:14][C:15](=[O:30])[NH:16][C@H:17]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:18][CH2:19][C:20]([OH:22])=[O:21])[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[CH3:31][C:32]([OH:34])=[O:33].[CH:35]([C:37]1[N:38]([CH2:42][C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH:39]=[CH:40][N:41]=1)=O.[BH-](O[C:60]([CH3:62])=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl>[C:46]([O:33][C:32](=[O:34])[CH2:31][N:38]1[CH:39]=[CH:40][N:41]=[C:60]1[CH2:62][N:1]([CH2:35][C:37]1[N:38]([CH2:42][C:43](=[O:44])[O:45][C:46]([CH3:49])([CH3:48])[CH3:47])[CH:39]=[CH:40][N:41]=1)[CH2:2][CH2:3][CH2:4][CH2:5][C@H:6]([NH:14][C:15](=[O:30])[NH:16][C@H:17]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:18][CH2:19][C:20]([OH:22])=[O:21])[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])([CH3:49])([CH3:48])[CH3:47]

참가 물질

6

반응물 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 58291458tert-butyl 2-(2-formyl-1H-imidazol-1-yl)acetateHCID 59404303(S)-4-(3-((S)-6-amino-1-tert-butoxy-1-oxohexan-2-yl)ureido)-5-tert-butoxy-5-oxopentanoic acid

생성물 1

HCID 59404337(S)-4-(3-((S)-6-(bis((1-(2-tert-butoxy-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)-1-tert-butoxy-1-oxohexan-2-yl)ureido)-5-tert-butoxy-5-oxopentanoic acid수율 52%

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매

반응 조건

온도
0 °C

실험 절차

A solution of (S)-4-(3-((S)-6-amino-1-tert-butoxy-1-oxohexan-2-yl)ureido)-5-tert-butoxy-5-oxopentanoic acid (432 mg, 70% pure, 0.70 mmol), AcOH (0.10 mL) and tert-butyl 2-(2-formyl-1H-imidazol-1-yl)acetate (470 mg, 2.0 mmol) in DCE (20 mL) was stirred at 75° C. for 30 min under nitrogen. The reaction mixture was cooled to 0° C., and treated with NaBH(OAc)3 (0.633 g, 3.0 mmol). The reaction was allowed to proceed overnight with stirring at room temperature. The reaction mixture was quenched with water and concentrated under reduced pressure to afford a residue which was purified by on a Biotage SP4 utilizing a gradient of 5-50% MeOH in DCM to afford (S)-4-(3-((S)-6-(bis((1-(2-tert-butoxy-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)-1-tert-butoxy-1-oxohexan-2-yl)ureido)-5-tert-butoxy-5-oxopentanoic acid (300 mg, 52%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 6.99 (s, 2H), 6.84 (s, 2H), 4.57 (s, 4H), 4.29-4.19 (m, 2H), 3.66-3.56 (m, 4H), 2.98-2.90 (m, 2H), 2.49-2.37 (m, 4H), 1.95-1.41 (m, 42H); ESMS m/z: 410.8 (M/2+H)+.

후처리

  1. customThe reaction mixture was quenched with water
  2. concentrationconcentrated under reduced pressure
  3. customto afford a residue which
  4. customwas purified by on a Biotage

출처 및 근거

ORD 기록
ord-c902268b6068489f826bf0baf12919d5
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08211402B2

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