Diisopropylethylamine → 4-[(2-{[3-({3-[(4-{2-[4-(Methoxycarbonyl)phenyl]ethyl}phenyl)carbamoyl]-4,5,6,7-tetrahydro-1-benzothiophen-2-yl}carbamoyl)benzyl](pentan-3-yl)amino)ethyl)(methyl)amino]-2,2-dimethyl-4-oxobutanoic acid

HRID 2176010Notes

Reaction equation

HRID 2176010 reaction equation
[CH3:1][NH:2][CH2:3][CH2:4][N:5]([CH2:11][C:12]1[CH:13]=[C:14]([CH:48]=[CH:49][CH:50]=1)[C:15]([NH:17][C:18]1[S:19][C:20]2[CH2:47][CH2:46][CH2:45][CH2:44][C:21]=2[C:22]=1[C:23]([NH:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][C:34]2[CH:43]=[CH:42][C:37]([C:38]([O:40][CH3:41])=[O:39])=[CH:36][CH:35]=2)=[CH:28][CH:27]=1)=[O:24])=[O:16])[CH:6]([CH2:9][CH3:10])[CH2:7][CH3:8].C(N(C(C)C)C(C)C)C.[CH3:60][C:61]1([CH3:68])[CH2:65][C:64](=[O:66])[O:63][C:62]1=[O:67]>O1CCOCC1>[CH3:41][O:40][C:38]([C:37]1[CH:42]=[CH:43][C:34]([CH2:33][CH2:32][C:29]2[CH:28]=[CH:27][C:26]([NH:25][C:23]([C:22]3[C:21]4[CH2:44][CH2:45][CH2:46][CH2:47][C:20]=4[S:19][C:18]=3[NH:17][C:15]([C:14]3[CH:13]=[C:12]([CH:50]=[CH:49][CH:48]=3)[CH2:11][N:5]([CH:6]([CH2:9][CH3:10])[CH2:7][CH3:8])[CH2:4][CH2:3][N:2]([CH3:1])[C:64](=[O:66])[CH2:65][C:61]([CH3:68])([CH3:60])[C:62]([OH:63])=[O:67])=[O:16])=[O:24])=[CH:31][CH:30]=2)=[CH:35][CH:36]=1)=[O:39]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 870672,2-Dimethylsuccinic anhydrideHCID 90370366HCID 90370366, compound

Product 1

HCID 903701804-[(2-{[3-({3-[(4-{2-[4-(Methoxycarbonyl)phenyl]ethyl}phenyl)carbamoyl]-4,5,6,7-tetrahydro-1-benzothiophen-2-yl}carbamoyl)benzyl](pentan-3-yl)amino)ethyl)(methyl)amino]-2,2-dimethyl-4-oxobutanoic acidYield 84.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

Procedure

To a mixture of 200 mg of methyl 4-[2-(4-{[(2-{[3-({[2-(methylamino)ethyl](pentan-3-yl)amino}methyl)benzoyl]amino}-4,5,6,7-tetrahydro-1-benzothiophen-3-yl)carbonyl]amino}phenyl)ethyl]benzoate, 48 mg of N-ethyl-N-isopropylpropan-2-amine and 4 mL of dioxane was added 44 mg of 3,3-dimethyldihydrofuran-2,5-dione, followed by stirring overnight at 65° C. The reaction mixture was concentrated under reduced pressure, ethyl acetate and water were added to the residue, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography, thereby obtaining 200 mg of 4-[(2-{[3-({3-[(4-{2-[4-(methoxycarbonyl)phenyl]ethyl}phenyl)carbamoyl]-4,5,6,7-tetrahydro-1-benzothiophen-2-yl}carbamoyl)benzyl](pentan-3-yl)amino}ethyl)(methyl)amino]-2,2-dimethyl-4-oxobutanoic acid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, ethyl acetate and water
  2. additionwere added to the residue
  3. extractionfollowed by extraction with ethyl acetate
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-bb299870febe41728ca5dc1349edb6b0
Source dataset
uspto-grants-2015_06
Patent number
US09062032B2

Reaction notes

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