Diisopropylethylamine → methyl 4-{2-[4-({[2-({3-[(4S)-4,7-dimethyl-3,6-dioxo-10-(pentan-3-yl)-2-oxa-5,7,10-triazaundecan-11-yl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl)amino)phenyl]ethyl}benzoate

HRID 2175996Notes

Reaction equation

HRID 2175996 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.[N:60]([C@@H:63]([CH3:68])[C:64]([O:66][CH3:67])=[O:65])=[C:61]=[O:62].C(=O)([O-])O.[Na+]>C(OCC)(=O)C.C1COCC1>[CH3:68][C@H:63]([NH:60][C:61](=[O:62])[N:2]([CH3:1])[CH2:3][CH2:4][N:5]([CH:6]([CH2:9][CH3:10])[CH2:7][CH3:8])[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:35]=[CH:36][C:37]([C:38]([O:40][CH3:41])=[O:39])=[CH:42][CH:43]=2)=[CH:28][CH:27]=1)=[O:24])=[O:16])[C:64](=[O:65])[O:66][CH3:67]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 7019162methyl (2S)-2-isocyanatopropanoateHCID 90370366HCID 90370366, compound

Product 1

HCID 90370402methyl 4-{2-[4-({[2-({3-[(4S)-4,7-dimethyl-3,6-dioxo-10-(pentan-3-yl)-2-oxa-5,7,10-triazaundecan-11-yl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl)amino)phenyl]ethyl}benzoateYield 97.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 250 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, 0.20 mL of N-ethyl-N-isopropylpropan-2-amine and 10 mL of THF under ice cooling was added 70 mg of methyl(S)-(−)-2-isocyanatopropionate, followed by stirring for 1 hour at the same temperature and then for 2 hours at room temperature. Ethyl acetate and an aqueous sodium hydrogen carbonate solution were added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (10% methanol/chloroform), thereby obtaining 290 mg methyl 4-{2-[4-({[2-({3-[(4S)-4,7-dimethyl-3,6-dioxo-10-(pentan-3-yl)-2-oxa-5,7,10-triazaundecan-11-yl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoate.

Workup

  1. waitfor 2 hours at room temperature
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (10% methanol/chloroform)

Sources & evidence

ORD record
ord-c6e17f72b0974e5694faa8e814561632
Source dataset
uspto-grants-2015_06
Patent number
US09062032B2

Reaction notes

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