(+-)-Mercaptosuccinic acid → 2-[3'-(5-Carbamimidoyl-2-methylsulfanyl-thiophene-3-sulfonyl)-6-methyl-biphenyl-2-ylmethylsulfanyl]-succinic acid trifluoracetate

HRID 723186Notes

Reaction equation

HRID 723186 reaction equation
[SH:1][CH:2]([CH2:6][C:7]([OH:9])=[O:8])[C:3]([OH:5])=[O:4].C(OC([NH:17][C:18](=[NH:48])[C:19]1[S:23][C:22]([S:24][CH3:25])=[C:21]([S:26]([C:29]2[CH:30]=[C:31]([C:35]3[C:40]([CH3:41])=[CH:39][CH:38]=[CH:37][C:36]=3[CH2:42]OS(C)(=O)=O)[CH:32]=[CH:33][CH:34]=2)(=[O:28])=[O:27])[CH:20]=1)=O)(C)(C)C.C(N(CC)CC)C.C(Cl)(Cl)Cl.[F:60][C:61]([F:66])([F:65])[C:62]([OH:64])=[O:63]>ClCCl>[F:60][C:61]([F:66])([F:65])[C:62]([OH:64])=[O:63].[C:18]([C:19]1[S:23][C:22]([S:24][CH3:25])=[C:21]([S:26]([C:29]2[CH:30]=[C:31]([C:35]3[C:40]([CH3:41])=[CH:39][CH:38]=[CH:37][C:36]=3[CH2:42][S:1][CH:2]([CH2:6][C:7]([OH:9])=[O:8])[C:3]([OH:5])=[O:4])[CH:32]=[CH:33][CH:34]=2)(=[O:27])=[O:28])[CH:20]=1)(=[NH:17])[NH2:48]

Participants

6

Reactant 4

HCID 6268(+-)-Mercaptosuccinic acidHCID 8471TriethylamineHCID 19978452Chloroform trifluoroacetic acidHCID 145857637[3-methyl-2-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]phenyl]methyl methanesulfonate

Product 1

HCID 695865612-[3'-(5-Carbamimidoyl-2-methylsulfanyl-thiophene-3-sulfonyl)-6-methyl-biphenyl-2-ylmethylsulfanyl]-succinic acid trifluoracetateYield 42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-Mercapto-succinic acid (0.004 g, 0.028 mmol) was added to a solution of methanesulfonic acid 3′-[5-(tert-butoxycarbonylamino-imino-methyl)-2-methylsulfanyl-thiophene-3-sulfonyl]-6-methyl-biphenyl-2-ylmethyl ester (0.017 g, 0.028 mmol) [example 214, step a] and triethylamine (0.009 g, 0.084 mmol) in dichloromethane [0.5 mL] at 40° C., stirred for 2 hours and then evaporated. The crude reaction was dissolved in a solution of dichloromethane/trifluoroacetic acid (1/1) [2 mL] and stirred for 1 hour. The reaction mixture was evaporated and purified via reverse-phase HPLC [acetonitrile/water (0.01% TFA)] to give the title compound (0.005 g, 42%) as a solid. 1H-NMR (MeOD): δ 8.31 (s, 1H), 8.06 (t, 1H, J=8.0 Hz), 7.83 (d, 1H, J=16.8 Hz), 7.70 (q, 1H, J=6.8 Hz), 7.57 (t, 1H, J=7.2 Hz), 7.29–7.21 (m, 3H), 3.60–3.48 (m, 1H), 3.54 (s, 3H), 3.37–3.34 (m, 1H), 2.70 (s, 3H), 2.68–2.57 (m, 1H), 2.31–2.14 (m, 1H), 1.97 (s, 3H). ESI-MS (m/z): Calcd. for C24H24N2O6S4: 564.05; found: 565.1.

Workup

  1. customevaporated
  2. customThe crude reaction
  3. stirringstirred for 1 hour
  4. customThe reaction mixture was evaporated
  5. custompurified via reverse-phase HPLC [acetonitrile/water (0.01% TFA)]

Sources & evidence

ORD record
ord-c256f53517db4a2d949cb918b5078c06
Source dataset
uspto-grants-2006_11
Patent number
US07138530B2

Reaction notes

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