Triethylamine → methyl 6-[5-amino-3-methyl-2-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]anilino]-6-oxohexanoate

HRID 2216163Notes

Reaction equation

HRID 2216163 reaction equation
[C:1]([O:5][C:6](=[O:37])[NH:7][C:8]([C:10]1[S:11][C:12]([S:35][CH3:36])=[C:13]([S:15]([C:18]2[CH:19]=[C:20]([C:24]3[C:29]([NH2:30])=[CH:28][C:27]([N+:31]([O-])=O)=[CH:26][C:25]=3[CH3:34])[CH:21]=[CH:22][CH:23]=2)(=[O:17])=[O:16])[CH:14]=1)=[NH:9])([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.[CH3:45][O:46][C:47](=[O:55])[CH2:48][CH2:49][CH2:50][CH2:51][C:52](Cl)=[O:53]>C(Cl)Cl>[CH3:45][O:46][C:47](=[O:55])[CH2:48][CH2:49][CH2:50][CH2:51][C:52](=[O:53])[NH:30][C:29]1[CH:28]=[C:27]([NH2:31])[CH:26]=[C:25]([CH3:34])[C:24]=1[C:20]1[CH:21]=[CH:22][CH:23]=[C:18]([S:15]([C:13]2[CH:14]=[C:10]([C:8]([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:37])=[NH:9])[S:11][C:12]=2[S:35][CH3:36])(=[O:17])=[O:16])[CH:19]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 520737Methyl 6-chloro-6-oxohexanoateHCID 145857628tert-butyl N-[4-[3-(2-amino-6-methyl-4-nitrophenyl)phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

Product 1

HCID 145857655methyl 6-[5-amino-3-methyl-2-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]anilino]-6-oxohexanoateYield 23.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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) 130 mg, 0.23 mmol), and Et3N (192 μL, 1.38 mmol) in DCM (5 mL) at 0° C. was added 5-chlorocarbonyl-pentanoic acid methyl ester (53 mg, 0.29). After stirring for 1 h, the solution was partitioned between EtOAc (70 mL) and aq NH4Cl (30 mL) and the layers were separated. The organic layer was washed with NaHCO3 (20 mL) and brine (30 mL) and was dried over sodium sulfate. The solution was concentrated and the residue was purified by SiO2 flash column chromatography to yield 36 mg of the amide product. The residue dissolved in EtOH (5 mL). Saturated aqueous NH4Cl (1.5 mL) was added followed by iron powder (110 mg, 2 mmol). The mixture was vigorously stirred at 80° C. for 30 min. The solution was filtered through a 0.22 μm filter and was then partitioned between EtOAc (70 mL) and water (20 mL). The layers were separated, the organic solution was dried over sodium sulfate, and the solution was concentrated to give the crude title compound which was used without further purification. 1H-NMR (CDCl3): δ 8.0 (m, 2H), 7.84 (s, 1H), 7.96 (m, 2H), 7.59 (t, 1H, J=7.7 Hz), 7.43 (m, 1H), 7.23 (br s, 1H), 6.86 (br s, 1H), 6.45 (br s, 1H), 3.85 (br s, 2H), 3.65 (s, 3H), 2.60 (m, 3H), 2.35 (m, 2H), 2.00 (m, 2H), 1.90 (s, 3H), 1.67 (m, 2H), 1.90 (s, 3H), 1.53 (s, 9H).

Workup

  1. customthe solution was partitioned between EtOAc (70 mL) and aq NH4Cl (30 mL)
  2. customthe layers were separated
  3. washThe organic layer was washed with NaHCO3 (20 mL) and brine (30 mL)
  4. dry with materialwas dried over sodium sulfate
  5. concentrationThe solution was concentrated
  6. customthe residue was purified by SiO2 flash column chromatography

Sources & evidence

ORD record
ord-5d118cfc70154bb7b109a95ea0b983ac
Source dataset
uspto-grants-2006_09
Patent number
US07109354B2

Reaction notes

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