Acetic Acid → di-tert-butyl 2,2'-((2-(2-((((1-(2-((3-iodophenyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)(4-sulfamoylphenethyl)amino)methyl)-1H-imidazo 1-yl)acetyl)azanediyl)diacetate

HRID 2273349Notes

Reaction equation

HRID 2273349 reaction equation
[S:1]([C:5]1[CH:39]=[CH:38][C:8]([CH2:9][CH2:10][NH:11][CH2:12][C:13]2[N:14]([CH2:18][C:19]([N:21]([CH2:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[O:20])[CH:15]=[CH:16][N:17]=2)=[CH:7][CH:6]=1)(=[O:4])(=[O:3])[NH2:2].CC(O)=O.[CH:44]([C:46]1[N:47]([CH2:51][C:52]([NH:54][C:55]2[CH:60]=[CH:59][CH:58]=[C:57]([I:61])[CH:56]=2)=[O:53])[CH:48]=[CH:49][N:50]=1)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.O>[I:61][C:57]1[CH:56]=[C:55]([NH:54][C:52](=[O:53])[CH2:51][N:47]2[CH:48]=[CH:49][N:50]=[C:46]2[CH2:44][N:11]([CH2:12][C:13]2[N:14]([CH2:18][C:19]([N:21]([CH2:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:22][C:23]([O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:24])=[O:20])[CH:15]=[CH:16][N:17]=2)[CH2:10][CH2:9][C:8]2[CH:38]=[CH:39][C:5]([S:1](=[O:3])(=[O:4])[NH2:2])=[CH:6][CH:7]=2)[CH:60]=[CH:59][CH:58]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 71521810di-tert-butyl 2,2'-((2-(2-(((4-sulfamoylphenethyl)amino)methyl)-1H-imidazol-1-yl)acetyl)azanediyl)diacetateHCID 866927222-(2-formyl-1H-imidazol-1-yl)-N-(3-iodophenyl)acetamide

Product 1

HCID 86692723di-tert-butyl 2,2'-((2-(2-((((1-(2-((3-iodophenyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)(4-sulfamoylphenethyl)amino)methyl)-1H-imidazo 1-yl)acetyl)azanediyl)diacetateYield 56.1%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of di-tert-butyl 2,2′-((2-(2-(((4-sulfamoylphenethyl)amino)methyl)-1H-imidazol-1-yl)acetyl)azanediyl)diacetate (283 mg, 0.50 mmol), AcOH (0.10 mL) and 2-(2-formyl-1H-imidazol-1-yl)-N-(3-iodophenyl)acetamide (178 mg, 0.50 mmol) in DCE (20 mL) at 0° C. was added NaBH(OAc)3 (0.30 g, 1.5 mmol). The reaction mixture was stirred at 0° C. for 30 minutes and at room temperature for overnight and decomposed with water. The reaction mixture was extracted with DCM. The organic layer was dried and concentrated under reduced pressure. The residue was purified by biotage over silica gel eluting with DCM to 40% MeOH in DCM to afford di-tert-butyl 2,2′-((2-(2-((((1-(2-((3-iodophenyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)(4-sulfamoylphenethyl)amino)methyl)-1H-imidazol-1-yl)acetyl)azanediyl)diacetate (254 mg, 56%).

Workup

  1. extractionThe reaction mixture was extracted with DCM
  2. customThe organic layer was dried
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by biotage over silica gel eluting with DCM to 40% MeOH in DCM

Sources & evidence

ORD record
ord-a11bfea6f58b44fa9b2f1155b258fb96
Source dataset
uspto-grants-2015_09
Patent number
US09120837B2

Reaction notes

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