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

Reaction equation

HRID 56323 reaction equation
[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]

Participants

6

Reactant 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

Product 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 acidYield 52%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-b5a8f553933049f19f1fd62d567d2885
Source dataset
uspto-grants-2016_09
Patent number
US09433594B2

Linked notes

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