Triethylamine → ethyl 6-[[3-[(5-methoxy-5-oxopentanoyl)amino]-5-methyl-4-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]phenyl]carbamoylamino]hexanoate

HRID 2216173Notes

Reaction equation

HRID 2216173 reaction equation
[CH3:1][O:2][C:3](=[O:10])[CH2:4][CH2:5][CH2:6][C:7](Cl)=[O:8].[CH2:11]([O:13][C:14](=[O:58])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][NH:20][C:21]([NH:23][C:24]1[CH:29]=[C:28]([CH3:30])[C:27]([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([S:37]([C:40]3[CH:44]=[C:43]([C:45]([NH:47][C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])=[NH:46])[S:42][C:41]=3[S:55][CH3:56])(=[O:39])=[O:38])[CH:32]=2)=[C:26]([NH2:57])[CH:25]=1)=[O:22])[CH3:12].C(N(CC)CC)C>C(Cl)Cl.CCOC(C)=O>[CH2:11]([O:13][C:14](=[O:58])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][NH:20][C:21]([NH:23][C:24]1[CH:29]=[C:28]([CH3:30])[C:27]([C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([S:37]([C:40]3[CH:44]=[C:43]([C:45]([NH:47][C:48]([O:50][C:51]([CH3:52])([CH3:53])[CH3:54])=[O:49])=[NH:46])[S:42][C:41]=3[S:55][CH3:56])(=[O:39])=[O:38])[CH:32]=2)=[C:26]([NH:57][C:7](=[O:8])[CH2:6][CH2:5][CH2:4][C:3]([O:2][CH3:1])=[O:10])[CH:25]=1)=[O:22])[CH3:12]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 73916Methyl 4-chloroformylbutyrateHCID 145857638ethyl 6-[[3-amino-5-methyl-4-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]phenyl]carbamoylamino]hexanoate

Product 1

HCID 145857701ethyl 6-[[3-[(5-methoxy-5-oxopentanoyl)amino]-5-methyl-4-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]phenyl]carbamoylamino]hexanoateYield 55.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Chlorocarbonyl-butyric acid methyl ester (20.4 μL, 0.148 mmol) was added to a solution of 6-(3-{2-amino-3′-[5-(tert-butoxycarbonylamino-imino-methyl)-2-methylsulfanyl-thiophene-3-sulfonyl]-6-methyl-biphenyl-4-yl}-ureido)-hexanoic acid ethyl ester (70.8 mg, 96.4 μmol, Example 278: step c) and triethylamine (41.2 μL, 0.296 mmol) in CH2Cl2 (5 mL, anhydrous) at rt. The reaction mixture was stirred overnight at rt, then diluted in EtOAc, washed with water and brine, and dried over magnesium sulfate. Removal of solvents in vacuo followed by flash chromatography (75–100% EtOAc/hexanes) yielded the title compound as a brown oil (45.5 mg, 54.5%). ESI-MS (m/z): Calcd. for C39H51N5O10S3: 846.3 (M+1); found: 845.9.

Workup

  1. washwashed with water and brine
  2. dry with materialdried over magnesium sulfate
  3. customRemoval of solvents in vacuo

Sources & evidence

ORD record
ord-eb66bcbb25f14e87bbe0deaea8b3924c
Source dataset
uspto-grants-2006_09
Patent number
US07109354B2

Reaction notes

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