1,2-Dichloroethane → (5s)-2-(2-(4-Tert-butylpiperazin-1-yl)-3,5-difluorophenyl)-3-(3,3-dimethylbutyl)-5-(2-oxo-2-(4-(2-oxo-2,3-dihydro-1h-benzo[d]imidazol-1-yl)piperidin-1-yl)ethyl)thiazolidin-4-one

HRID 1695920Notes

Reaction equation

HRID 1695920 reaction equation
[C:1]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[C:16]([F:17])=[CH:15][C:14]([F:18])=[CH:13][C:12]=2[CH:19]2[N:23]([CH2:24][CH2:25][C:26]([CH3:29])([CH3:28])[CH3:27])[C:22](=[O:30])[C@H:21]([CH2:31][C:32](O)=[O:33])[S:20]2)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[CH2:35](Cl)[CH2:36]Cl.CCN(C(C)C)C(C)C.Cl.Cl.[NH:50]1[CH2:55][CH2:54][CH:53]([N:56]2[C:64]3C(=N[CH:61]=[CH:62][CH:63]=3)[NH:58][C:57]2=[O:65])[CH2:52][CH2:51]1>CN(C=O)C.CCOC(C)=O>[C:1]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[C:16]([F:17])=[CH:15][C:14]([F:18])=[CH:13][C:12]=2[CH:19]2[N:23]([CH2:24][CH2:25][C:26]([CH3:28])([CH3:27])[CH3:29])[C:22](=[O:30])[C@H:21]([CH2:31][C:32](=[O:33])[N:50]3[CH2:51][CH2:52][CH:53]([N:56]4[C:64]5[CH:63]=[CH:62][CH:61]=[CH:35][C:36]=5[NH:58][C:57]4=[O:65])[CH2:54][CH2:55]3)[S:20]2)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 222931811-(piperidin-4-yl)-1H,2H,3H-imidazo[4,5-b]pyridin-2-one dihydrochlorideHCID 577744422-((5S)-2-(2-(4-tert-butylpiperazin-1-yl)-3,5-difluorophenyl)-3-(3,3-dimethylbutyl)-4-oxothiazolidin-5-yl)acetic acid

Product 1

HCID 57774425(5s)-2-(2-(4-Tert-butylpiperazin-1-yl)-3,5-difluorophenyl)-3-(3,3-dimethylbutyl)-5-(2-oxo-2-(4-(2-oxo-2,3-dihydro-1h-benzo[d]imidazol-1-yl)piperidin-1-yl)ethyl)thiazolidin-4-oneYield 15%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-((5S)-2-(2-(4-tert-Butylpiperazin-1-yl)-3,5-difluorophenyl)-3-(3,3-dimethylbutyl)-4-oxothiazolidin-5-yl)acetic acid (100 mg, 0.2 mmol), EDC (40 mg, 0.2 mmol), DIEA (52 mg, 0.4 mmol) and 1-(piperidin-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one bis HCl salt (60 mg, 0.2 mmol) were combined in DMF and let stir for 3 days. The mixture was then poured into EtOAc/sat'd NaHCO3. The organic layer was dried and concentrated to a solid and purified by reverse phase HPLC. Pure fractions were poured into EtOAc/1N NaOH and the organic layer was dried and concentrated to a solid, which was taken up in methanol. Then 4N HCl in dioxane was added. This solution was concentrated to give (5S)-2-(2-(4-tert-butylpiperazin-1-yl)-3,5-difluorophenyl)-3-(3,3-dimethylbutyl)-5-(2-oxo-2-(4-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)ethyl)thiazolidin-4-one as a white solid (24 mg., 0.03 mmol, 15% yield). LC/MS MH+ 697.97.

Workup

  1. customThe organic layer was dried
  2. concentrationconcentrated to a solid
  3. custompurified by reverse phase HPLC
  4. additionPure fractions were poured into EtOAc/1N NaOH
  5. customthe organic layer was dried
  6. concentrationconcentrated to a solid, which
  7. additionThen 4N HCl in dioxane was added
  8. concentrationThis solution was concentrated

Sources & evidence

ORD record
ord-52cf064c496447d59beaaad773a48674
Source dataset
uspto-grants-2012_04
Patent number
US08163737B2

Reaction notes

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