Acetic Acid → di-tert-butyl 4-(2-(2-((((1-(2-(bis(2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)(4-sulfamoylphenethyl)amino)methyl)-1H-imidazol-1-yl)acetamido)-4-(3-(tert-butoxy)-3-oxopropyl)heptanedioate

HRID 2273342Notes

Reaction equation

HRID 2273342 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].[C:40]([O:44][C:45](=[O:78])[CH2:46][CH2:47][C:48]([NH:67][C:68](=[O:77])[CH2:69][N:70]1[CH:74]=[CH:73][N:72]=[C:71]1[CH:75]=O)([CH2:58][CH2:59][C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[CH2:49][CH2:50][C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])([CH3:43])([CH3:42])[CH3:41].CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.O>[C:26]([O:25][C:23](=[O:24])[CH2:22][N:21]([CH2:30][C:31](=[O:32])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C:19](=[O:20])[CH2:18][N:14]1[CH:15]=[CH:16][N:17]=[C:13]1[CH2:12][N:11]([CH2:75][C:71]1[N:70]([CH2:69][C:68]([NH:67][C:48]([CH2:58][CH2:59][C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])([CH2:47][CH2:46][C:45]([O:44][C:40]([CH3:41])([CH3:42])[CH3:43])=[O:78])[CH2:49][CH2:50][C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])=[O:77])[CH:74]=[CH:73][N:72]=1)[CH2:10][CH2:9][C:8]1[CH:38]=[CH:39][C:5]([S:1](=[O:3])(=[O:4])[NH2:2])=[CH:6][CH:7]=1)([CH3:27])([CH3:28])[CH3:29]

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 86692716di-tert-butyl 4-(3-(tert-butoxy)-3-oxopropyl)-4-(2-(2-formyl-1H-imidazol-1-yl)acetamido)heptanedioate

Product 1

HCID 71521729di-tert-butyl 4-(2-(2-((((1-(2-(bis(2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)(4-sulfamoylphenethyl)amino)methyl)-1H-imidazol-1-yl)acetamido)-4-(3-(tert-butoxy)-3-oxopropyl)heptanedioateYield 61%

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 (200 mg, 0.353 mmol), di-tert-butyl 4-(3-(tert-butoxy)-3-oxopropyl)-4-(2-(2-formyl-1H-imidazol-1-yl)acetamido)heptanedioate (195 mg, 0.353 mmol), AcOH (0.10 mL) in DCE (10 mL) at 0° C. was treated with NaBH(OAc)3 (148 mg, 0.70 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 concentrated under reduced pressure to give a residue. The residue was purified by biotage over silica gel to afford di-tert-butyl 4-(2-(2-((((1-(2-(bis(2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)(4-sulfamoylphenethyl)amino)methyl)-1H-imidazol-1-yl)acetamido)-4-(3-(tert-butoxy)-3-oxopropyl)heptanedioate (237 mg, 61%). 1H NMR (400 MHz, DMSO-d6) 7.76 (s, 1H), 7.66 (d, J=8.4 Hz, 1H), 7.23 (d, J=8.4 Hz, 2H), 7.22 (s, 2H), 7.01 (d, J=1.2 Hz, 1H), 6.99 (d, J=1.6 Hz, 2H), 6.83 (d, J=0.8 Hz, 1H), 6.80 (d, J=0.8 Hz, 1H), 5.02 (s, 2H), 4.55 (s, 2H), 4.31 (s, 2H), 3.97 (s, 2H), 3.63 (s, 2H), 3.60 (s, 2H), 2.77-2.73 (m, 2H), 2.66-2.60 (m, 2H), 2.10 (t, J=8.2 Hz, 6H), 1.78 (t, J=8.2 Hz, 6H), 1.36 (s, 45H); MS (ESI), 551.4 (M/2+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto give a residue
  3. customThe residue was purified by biotage over silica gel

Sources & evidence

ORD record
ord-d40de91a4cd54779bd8212fb191e3dfb
Source dataset
uspto-grants-2015_09
Patent number
US09120837B2

Reaction notes

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