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 56323

反応式

HRID 56323 の反応式
[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]

参加物

6

反応物 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

生成物 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 acid収率 52%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

反応条件

温度
0 °C

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-b5a8f553933049f19f1fd62d567d2885
出典データセット
uspto-grants-2016_09
特許番号
US09433594B2

関連ノート

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