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-4,5-dihydro-1H-benzo[d][1,3]diazepin-3 (2H)-yl)piperidin-1-yl)ethyl)thiazolidin-4-one hydrochloride

HRID 1695921Notes

Reaction equation

HRID 1695921 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].C(Cl)C[Cl:37].C1C=CC2N(O)N=NC=2C=1.[NH:49]1[CH2:54][CH2:53][CH:52]([N:55]2[CH2:61][CH2:60][C:59]3[CH:62]=[CH:63][CH:64]=[CH:65][C:58]=3[NH:57][C:56]2=[O:66])[CH2:51][CH2:50]1.Cl>CN(C=O)C.O1CCOCC1.CO.CCOC(C)=O>[ClH:37].[C:1]([N:5]1[CH2:6][CH2:7][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]([CH3:27])([CH3:29])[CH3:28])[C:22](=[O:30])[C@H:21]([CH2:31][C:32](=[O:33])[N:49]3[CH2:50][CH2:51][CH:52]([N:55]4[CH2:61][CH2:60][C:59]5[CH:62]=[CH:63][CH:64]=[CH:65][C:58]=5[NH:57][C:56]4=[O:66])[CH2:53][CH2:54]3)[S:20]2)[CH2:9][CH2:10]1)([CH3:3])([CH3:4])[CH3:2]

Participants

10

Reactant 5

HCID 111,2-DichloroethaneHCID 313Hydrochloric Acid2×HCID 757711-HydroxybenzotriazoleHCID 113795873-(Piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-oneHCID 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 86632317(5S)-2-(2-(4-tert-butylpiperazin-1-yl)-3,5-difluorophenyl)-3-(3,3-dimethylbutyl)-5-(2-oxo-2-(4-(2-oxo-4,5-dihydro-1H-benzo[d][1,3]diazepin-3 (2H)-yl)piperidin-1-yl)ethyl)thiazolidin-4-one hydrochlorideYield 50%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

2-((5S)-2-(2-(4-tert-Butylpiperazin-1-yl)-3,5-difluorophenyl)-3-(3,3-dimethylbutyl)-4-oxothiazolidin-5-yl)acetic acid (60 mg, 0.12 mmol), EDC (23 mg, 0.12 mmol), HOBt (18 mg, 0.12 mmol), and 3-(piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-one (30 mg, 0.12 mmol) were combined in DMF and let stir for 16 hrs. The reaction mixture was poured into EtOAc/sat'd NaHCO3 and the organic layer dried and concentrated to a solid, which was purified by flash chromatography to give the product. The HCl salt was made with methanol plus 4N HCl in dioxane, to give (5S)-2-(2-(4-tert-butylpiperazin-1-yl)-3,5-difluorophenyl)-3-(3,3-dimethylbutyl)-5-(2-oxo-2-(4-(2-oxo-4,5-dihydro-1H-benzo[d][1,3]diazepin-3 (2H)-yl)piperidin-1-yl)ethyl)thiazolidin-4-one hydrochloride as a white solid (43 mg, 0.06 mmol, 50% yield). LC/MS MH+ 725.74.

Workup

  1. customthe organic layer dried
  2. concentrationconcentrated to a solid, which
  3. customwas purified by flash chromatography
  4. customto give the product

Sources & evidence

ORD record
ord-2ec8d137e71743eda794c239cb5b789b
Source dataset
uspto-grants-2012_04
Patent number
US08163737B2

Reaction notes

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