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

HRID 2176042Notes

Reaction equation

HRID 2176042 reaction equation
[N+](C1C=CC([O:8][C:9]([O:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])=O)=CC=1)([O-])=O.[CH3:19][NH:20][CH2:21][CH2:22][N:23]([CH2:29][C:30]1[CH:31]=[C:32]([CH:66]=[CH:67][CH:68]=1)[C:33]([NH:35][C:36]1[S:37][C:38]2[CH2:65][CH2:64][CH2:63][CH2:62][C:39]=2[C:40]=1[C:41]([NH:43][C:44]1[CH:49]=[CH:48][C:47]([CH2:50][CH2:51][C:52]2[CH:61]=[CH:60][C:55]([C:56]([O:58][CH3:59])=[O:57])=[CH:54][CH:53]=2)=[CH:46][CH:45]=1)=[O:42])=[O:34])[CH:24]([CH2:27][CH3:28])[CH2:25][CH3:26].C(N(C(C)C)C(C)C)C>C1COCC1>[CH3:19][N:20]([CH2:21][CH2:22][N:23]([CH:24]([CH2:25][CH3:26])[CH2:27][CH3:28])[CH2:29][C:30]1[CH:31]=[C:32]([CH:66]=[CH:67][CH:68]=1)[C:33]([NH:35][C:36]1[S:37][C:38]2[CH2:65][CH2:64][CH2:63][CH2:62][C:39]=2[C:40]=1[C:41]([NH:43][C:44]1[CH:49]=[CH:48][C:47]([CH2:50][CH2:51][C:52]2[CH:53]=[CH:54][C:55]([C:56]([O:58][CH3:59])=[O:57])=[CH:60][CH:61]=2)=[CH:46][CH:45]=1)=[O:42])=[O:34])[C:9](=[O:8])[O:11][CH2:12][C:13](=[O:14])[O:15][CH3:16]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 90370366HCID 90370366, compoundHCID 90377585Methyl {[(4-nitrophenoxy)carbonyl]oxy}acetate

Product 1

HCID 90370367Methyl 4-{2-[4-({[2-({3-[7-methyl-3,6-dioxo-10-(pentan-3-yl)-2,5-dioxa-7,10-diazaundecan-11-yl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoateYield 97.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of 100 mg of methyl {[(4-nitrophenoxy)carbonyl]oxy}acetate and 5.0 mL of THF was added to a mixture of 180 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, 0.15 mL of N-ethyl-N-isopropylpropan-2-amine, and 5.0 mL of THF under ice cooling, followed by stirring for 3 hours at room temperature. The reaction mixture was concentrated under reduced pressure, and ethyl acetate and a saturated aqueous sodium hydrogen carbonate solution were added to the residue, followed by extraction with ethyl acetate. The organic layer was washed sequentially with a saturated aqueous sodium hydrogen carbonate solution, water, and saturated brine and dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by basic silica gel column chromatography (hexane:chloroform=4:6), thereby obtaining 204 mg of methyl 4-{2-[4-({[2-({3-[7-methyl-3,6-dioxo-10-(pentan-3-yl)-2,5-dioxa-7,10-diazaundecan-11-yl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoate.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, and ethyl acetate
  2. additiona saturated aqueous sodium hydrogen carbonate solution were added to the residue
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed sequentially with a saturated aqueous sodium hydrogen carbonate solution, water, and saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was removed under reduced pressure
  7. customThe residue was purified by basic silica gel column chromatography (hexane:chloroform=4:6)

Sources & evidence

ORD record
ord-cbaa58b55a1b48c8a4947b199f586ea6
Source dataset
uspto-grants-2015_06
Patent number
US09062032B2

Reaction notes

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