Triethylamine → methyl 12-[5-amino-3-methyl-2-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]anilino]-12-oxododecanoate

HRID 2216205Notes

Reaction equation

HRID 2216205 reaction equation
C(N(CC)CC)C.[C:8]([O:12][C:13](=[O:44])[NH:14][C:15]([C:17]1[S:18][C:19]([S:42][CH3:43])=[C:20]([S:22]([C:25]2[CH:26]=[C:27]([C:31]3[C:36]([NH2:37])=[CH:35][C:34]([N+:38]([O-])=O)=[CH:33][C:32]=3[CH3:41])[CH:28]=[CH:29][CH:30]=2)(=[O:24])=[O:23])[CH:21]=1)=[NH:16])([CH3:11])([CH3:10])[CH3:9].[CH2:45]([O:47][C:48](=[O:62])[CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][C:59](Cl)=[O:60])C.C([O-])(O)=O.[Na+].[NH4+].[Cl-]>C(Cl)Cl.[Cl-].[Na+].O.CCO.[Fe].CCOC(C)=O>[CH3:45][O:47][C:48](=[O:62])[CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][C:59](=[O:60])[NH:37][C:36]1[CH:35]=[C:34]([NH2:38])[CH:33]=[C:32]([CH3:41])[C:31]=1[C:27]1[CH:28]=[CH:29][CH:30]=[C:25]([S:22]([C:20]2[CH:21]=[C:17]([C:15]([NH:14][C:13]([O:12][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:44])=[NH:16])[S:18][C:19]=2[S:42][CH3:43])(=[O:24])=[O:23])[CH:26]=1

Participants

11

Reactant 5

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 516892Sodium BicarbonateHCID 434365111-Ethoxycarbonyldodecanoyl chlorideHCID 145857628tert-butyl N-[4-[3-(2-amino-6-methyl-4-nitrophenyl)phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

Product 1

HCID 145857669methyl 12-[5-amino-3-methyl-2-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]anilino]-12-oxododecanoateYield 103.5%

Reagents, catalysts & solvents 5

HCID 23925IronCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
75 °C

Procedure

Triethylamine (139 μL, 1 mmol) was added to a solution of {[4-(6′-amino-2′-methyl-4′-nitro-biphenyl-3-sulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester ((Example 295: step h) 118 mg, 0.21 mmol) in DCM (10 mL). 11-chlorocarbonyl-undecanoic acid ethyl ester (73 mg, 0.26 mmol) was added dropwise over 5 min. After 30 minutes of stirring, the reaction was not complete. Additional portions of acid chloride (3×1 eq) were added in a similar manner, until the reaction was complete. Addition of EtOAc (40 mL) followed by aqueous workup with NaHCO3 (2×20 mL) and brine (30 mL) yielded the crude amide (206 mg) as a glass. The residue was dissolved in EtOH (5 mL) and 4M aq NH4Cl (1 mL) was added. Iron powder (165 mg, 3 mmol) was added and the reaction was heated at 75° C. for 1 h. The cooled mixture was filtered through a 0.22 μm filter and solids washed with 5 mL portions of MeOH and EtOAc. Additional EtOAc (80 mL) was added and the organic solution was washed with citric acid (2×20 mL), NaHCO3 (2×30 mL), water (30 mL), and brine (50 mL). Drying and concentration of the solution yielded the title compound (165 mg) which was used without further purification.

Workup

  1. customyielded the crude amide (206 mg) as a glass
  2. filtrationThe cooled mixture was filtered through a 0.22 μm
  3. filtrationfilter
  4. washsolids washed with 5 mL portions of MeOH and EtOAc
  5. additionAdditional EtOAc (80 mL) was added
  6. washthe organic solution was washed with citric acid (2×20 mL), NaHCO3 (2×30 mL), water (30 mL), and brine (50 mL)
  7. customDrying

Sources & evidence

ORD record
ord-5e9e5d0f583e44b2a18e2b973965dd9c
Source dataset
uspto-grants-2006_09
Patent number
US07109354B2

Reaction notes

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