Tetrahydrofuran → methyl 3-[3-methyl-2-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]anilino]-3-oxopropanoate

HRID 723093Notes

Reaction equation

HRID 723093 reaction equation
[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]([C:10]1[S:11][C:12]([S:32][CH3:33])=[C:13]([S:15]([C:18]2[CH:19]=[C:20]([C:24]3[C:29]([CH3:30])=[CH:28][CH:27]=[CH:26][C:25]=3[NH2:31])[CH:21]=[CH:22][CH:23]=2)(=[O:17])=[O:16])[CH:14]=1)=[NH:9])([CH3:4])([CH3:3])[CH3:2].C1COCC1.[CH3:40][O:41][C:42](=[O:47])[CH2:43][C:44](Cl)=[O:45]>CCOC(C)=O>[CH3:40][O:41][C:42](=[O:47])[CH2:43][C:44]([NH:31][C:25]1[CH:26]=[CH:27][CH:28]=[C:29]([CH3:30])[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:34])=[NH:9])[S:11][C:12]=2[S:32][CH3:33])(=[O:17])=[O:16])[CH:19]=1)=[O:45]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 123460Methyl malonyl chlorideHCID 145857623tert-butyl N-[4-[3-(2-amino-6-methylphenyl)phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

Product 1

HCID 145857671methyl 3-[3-methyl-2-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]anilino]-3-oxopropanoate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

{[4-(2′-Amino-6′-methyl-biphenyl-3-sulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester (22 mg, 0.04 mmol, Example 25: step c) was dissolved into THF (1 mL) and to this was added chlorocarbonyl-acetic acid methyl ester (9 μL, 0.085 mmol). The reaction was heated to 50° C. for 5 hours and then allowed to stir at RT for 48 hours. The reaction mixture was dissolved into EtOAc and washed with brine. The organic layers were dried (MgSO4) and removal of the solvents in vacuo was followed by purification by preparative TLC (SiO2) (30% EtOAc in hexanes) that yielded the title compound. ESI-MS (m/z): Calcd. for C28H31N3O7S3: 618.1 (M+1) found: 617.9.

Workup

  1. washwashed with brine
  2. customThe organic layers were dried
  3. custom(MgSO4) and removal of the solvents in vacuo
  4. customwas followed by purification by preparative TLC (SiO2) (30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-e5c8adb39e1545c3abc9129cda080ec9
Source dataset
uspto-grants-2006_11
Patent number
US07138530B2

Reaction notes

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