Hydrochloric Acid → (S)-2-{4'-[4-(4-Methanesulfonyl-piperazin-1-ylmethyl)-phenylcarbamoyl]-6-trifluoromethoxy-biphenyl-3-ylcarbamoyl}-azetidine-1-carboxylic acid

HRID 1678505Notes

Reaction equation

HRID 1678505 reaction equation
C([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[C:12](=[O:51])[NH:13][C:14]1[CH:15]=[C:16]([C:25]2[CH:30]=[CH:29][C:28]([C:31](=[O:50])[NH:32][C:33]3[CH:38]=[CH:37][C:36]([CH2:39][N:40]4[CH2:45][CH2:44][N:43]([S:46]([CH3:49])(=[O:48])=[O:47])[CH2:42][CH2:41]4)=[CH:35][CH:34]=3)=[CH:27][CH:26]=2)[C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:18][CH:19]=1)=[O:7])(C)(C)C.Cl.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1>[CH3:49][S:46]([N:43]1[CH2:44][CH2:45][N:40]([CH2:39][C:36]2[CH:37]=[CH:38][C:33]([NH:32][C:31]([C:28]3[CH:27]=[CH:26][C:25]([C:16]4[C:17]([O:20][C:21]([F:22])([F:24])[F:23])=[CH:18][CH:19]=[C:14]([NH:13][C:12]([C@@H:9]5[CH2:10][CH2:11][N:8]5[C:6]([OH:7])=[O:5])=[O:51])[CH:15]=4)=[CH:30][CH:29]=3)=[O:50])=[CH:34][CH:35]=2)[CH2:41][CH2:42]1)(=[O:48])=[O:47]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 67372397(S)-2-{4'-[4-(4-Methanesulfonyl-piperazin-1-ylmethyl)-phenylcarbamoyl]-6-trifluoromethoxy-biphenyl-3-ylcarbamoyl}-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 16222129(S)-2-{4'-[4-(4-Methanesulfonyl-piperazin-1-ylmethyl)-phenylcarbamoyl]-6-trifluoromethoxy-biphenyl-3-ylcarbamoyl}-azetidine-1-carboxylic acid

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of (S)-2-{4′-[4-(4-Methanesulfonyl-piperazin-1-ylmethyl)-phenylcarbamoyl]-6-trifluoromethoxy-biphenyl-3-ylcarbamoyl}-azetidine-1-carboxylic acid tert-butyl ester in dioxan (5 ml) was treated with conc. hydrochloric acid (3 ml) and the mixture stirred at room temp for 18 h. The mixture was then carefully basified with solid potassium carbonate and the mixture then was extracted with DCM. The residue was then purified on silica gel. Elution initially with DCM:EtOH:ammonia; 200:8:1 gave a colourless foam (impure). Further purification eluting with DCM:MeOH:AcOH:water; 90:10:1:1 gave a colourless gum (nmr suggests probably acetate salt of desired product). This material was then dissolved in DCM:EtOH:ammonia;25:8:1 and then passed down an SCX cartridge giving the title compound as a colourless solid (14 mg). This material is still not entirely pure as shown by 1H NMR. No further purification of this material was carried out.

Workup

  1. extractionthe mixture then was extracted with DCM
  2. customThe residue was then purified on silica gel
  3. washElution initially with DCM
  4. custom200:8:1 gave a colourless foam (impure)
  5. customFurther purification
  6. washeluting with DCM
  7. custom90:10:1:1 gave a colourless gum (nmr

Sources & evidence

ORD record
ord-159565143b1d44b499e968bbcb059403
Source dataset
uspto-grants-2011_08
Patent number
US08008303B2

Reaction notes

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