Methanol → 6-[3-methyl-2-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]anilino]-6-oxohexanoic acid

HRID 723104Notes

Reaction equation

HRID 723104 reaction equation
C[O:2][C:3](=[O:44])[CH2:4][CH2:5][CH2:6][CH2:7][C:8](=[O:43])[NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([CH3:16])[C:11]=1[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([S:23]([C:26]2[CH:30]=[C:29]([C:31]([NH:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])=[NH:32])[S:28][C:27]=2[S:41][CH3:42])(=[O:25])=[O:24])[CH:18]=1.[Li+].[OH-].CO>CCOC(C)=O>[C:37]([O:36][C:34]([NH:33][C:31](=[NH:32])[C:29]1[S:28][C:27]([S:41][CH3:42])=[C:26]([S:23]([C:19]2[CH:18]=[C:17]([C:11]3[C:12]([CH3:16])=[CH:13][CH:14]=[CH:15][C:10]=3[NH:9][C:8]([CH2:7][CH2:6][CH2:5][CH2:4][C:3]([OH:44])=[O:2])=[O:43])[CH:22]=[CH:21][CH:20]=2)(=[O:25])=[O:24])[CH:30]=1)=[O:35])([CH3:40])([CH3:38])[CH3:39]

Participants

5

Reactant 3

HCID 887MethanolHCID 3939Lithium HydroxideHCID 145857617methyl 6-[3-methyl-2-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]anilino]-6-oxohexanoate

Product 1

HCID 1458576736-[3-methyl-2-[3-[5-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]-2-methylsulfanylthiophen-3-yl]sulfonylphenyl]anilino]-6-oxohexanoic acid

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

5-{3′-[5-(tert-Butoxycarbonylamino-imino-methyl)-2-methylsulfanyl-thiophene-3-sulfonyl]-6-methyl-biphenyl-2-ylcarbamoyl}-pentanoic acid methyl ester (125 mg, 0.19 mmol, Example 137: step a) and LiOH (12.5 mg, 0.54 mmol) were dissolved into MeOH (3 mL) and heated to 60° C. for 12 hours. The reaction was dissolved into EtOAc and washed with 20% citric acid. The aqueous layers were acidified with acetic acid (pH 3) and extracted with EtOAc. The organic layers were combined and dried (MgSO4) followed by removal of solvents in vacuo. The resulting material was purified by preparative RP-HPLC (0–100% water/acetonitrile—both solvents were free of TFA, 45 minutes, λ=245 nm). 1H-NMR (CDCl3): δ 7.95–7.93 (d, 1H, J=9.3 Hz), 7.81–7.78 (d, 1H, J=7.91 Hz), 7.63–7.59 (m, 1H), 7.55–7.53 (t, 1H, J=8.35, Hz, J=7.59 Hz), 7.38–7.36 (d, 1H, J=9.35 Hz), 7.25–7.21 (m, 1H), 7.07–7.05 (d, 1H, J=7.07 Hz), 6.78 (s, 1H), 3.55 (s, 2H), 2.51 (s, 3H), 2.15–2.12 (m, 2H), 1.96–1.95 (m, 2H), 1.93 (s, 3H).

Workup

  1. washwashed with 20% citric acid
  2. extractionextracted with EtOAc
  3. dry with materialdried (MgSO4)
  4. customfollowed by removal of solvents in vacuo
  5. customThe resulting material was purified by preparative RP-HPLC (0–100% water/acetonitrile—both solvents
  6. customwere free of TFA, 45 minutes, λ=245 nm

Sources & evidence

ORD record
ord-c467c91e6f0b4d199aba895c7147b052
Source dataset
uspto-grants-2006_11
Patent number
US07138530B2

Reaction notes

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