Trifluoroacetic acid → 6-Chloro-N-(cyclohexylmethyl)-2-[(3S)-3-(1,1-dioxido-4-oxo-1,2,5-thiadiazolidin-2-yl)-1-pyrrolidinyl]-5-quinolinecarboxamide

HRID 2217919Notes

Reaction equation

HRID 2217919 reaction equation
[Cl:1][C:2]1[C:3]([C:35]([NH:37][CH2:38][CH:39]2[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]2)=[O:36])=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([N:12]1[CH2:16][CH2:15][C@H:14]([N:17]([S:24]([NH:27][C:28]([O:30]C(C)(C)C)=O)(=[O:26])=[O:25])[CH2:18]C(OCC)=O)[CH2:13]1)[CH:6]=[CH:5]2.FC(F)(F)C(O)=O>ClCCl>[Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[C:7]([N:12]3[CH2:16][CH2:15][C@H:14]([N:17]4[CH2:18][C:28](=[O:30])[NH:27][S:24]4(=[O:26])=[O:25])[CH2:13]3)[CH:6]=[CH:5][C:4]=2[C:3]=1[C:35]([NH:37][CH2:38][CH:39]1[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]1)=[O:36]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 131726985N-[(3S)-1-[6-Chloro-5-[[(cyclohexylmethyl)amino]carbonyl]-2-quinolinyl]-3-pyrrolidinyl]-N-[[[(1,1-dimethylethoxy)carbonyl]amino]sulfonyl]-glycine, Ethyl Ester

Product 1

HCID 112835256-Chloro-N-(cyclohexylmethyl)-2-[(3S)-3-(1,1-dioxido-4-oxo-1,2,5-thiadiazolidin-2-yl)-1-pyrrolidinyl]-5-quinolinecarboxamideYield 3.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-[(3S)-1-[6-Chloro-5-[[(cyclohexylmethyl)amino]carbonyl]-2-quinolinyl]-3-pyrrolidinyl]-N-[[[(1,1-dimethylethoxy)carbonyl]amino]sulfonyl]-glycine, ethyl ester (Example 112 (b)) (670 mg) was dissolved in dichloromethane (5 mL). Trifluoroacetic acid (1 mL) was added and the mixture stirred for 3 hours before being concentrated. Sodium methoxide (25% in methanol, 3 mL) was added and the mixture was stirred under nitrogen for 2 hours. The products were concentrated onto silica gel and purified by chromatography (SiO2, dichloromethane:methanol 92:8 as eluant). Further purification by HPLC (Symmetry—0.1% aqueous trifluoroacetic acid/acetonitrile) gave the title compound as a solid (20 mg).

Workup

  1. concentrationbefore being concentrated
  2. additionSodium methoxide (25% in methanol, 3 mL) was added
  3. stirringthe mixture was stirred under nitrogen for 2 hours
  4. concentrationThe products were concentrated onto silica gel
  5. custompurified by chromatography (SiO2, dichloromethane:methanol 92:8 as eluant)
  6. customFurther purification by HPLC (Symmetry—0.1% aqueous trifluoroacetic acid/acetonitrile)

Sources & evidence

ORD record
ord-47460db7ee904b99ace5e6679604b1c9
Source dataset
uspto-grants-2008_08
Patent number
US07408065B2

Reaction notes

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