Hydrochloric Acid → (5S)-2,2-dimethyl-5-((1S)-3-methyl-1-{[4-(3-phenyl-1,2,4-thiadiazol-5-yl)-1-piperazinyl]carbonyl}butyl)-1,3-dioxolan-4-one

HRID 888221Notes

Reaction equation

HRID 888221 reaction equation
[CH3:1][C:2]1([CH3:27])[O:6][C@@H:5]([C@H:7]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:8]([O:10]C2C(F)=C(F)C(F)=C(F)C=2F)=O)[C:4](=[O:26])[O:3]1.ONC(=O)[C@@H](O)[C@@H](C(N1CCN(C2C=CC=CN=2)CC1)=O)CC(C)C.[C:53]1([C:59]2[N:63]=[C:62]([N:64]3[CH2:69][CH2:68][NH:67][CH2:66][CH2:65]3)[S:61][N:60]=2)[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1.Cl>CN(C=O)C>[CH3:27][C:2]1([CH3:1])[O:3][C:4](=[O:26])[C@H:5]([C@@H:7]([C:8]([N:67]2[CH2:68][CH2:69][N:64]([C:62]3[S:61][N:60]=[C:59]([C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=4)[N:63]=3)[CH2:65][CH2:66]2)=[O:10])[CH2:22][CH:23]([CH3:24])[CH3:25])[O:6]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 27777601-(3-Phenyl-(1,2,4)thiadiazol-5-yl)-piperazineHCID 11653205HCID 11653205, compound2×HCID 86617975HCID 86617975, compound

Product 1

HCID 58487953(5S)-2,2-dimethyl-5-((1S)-3-methyl-1-{[4-(3-phenyl-1,2,4-thiadiazol-5-yl)-1-piperazinyl]carbonyl}butyl)-1,3-dioxolan-4-oneYield 5.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of a 55/45 diastereoisomeric mixture of pentafluorophenyl (2S)-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-4-methylpentanoate and pentafluorophenyl (2R)-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-4-methylpentanoate (Intermediate 1; 150.0 mg; 0.38 mmol; 1.0 eq.) in DMF (1.5 mL) was added 3-phenyl-5-piperazino-1,2,4-thiadiazole (93.2 mg; 0.38 mmol; 1.0 eq.) and the resulting reaction mixture was stirred at RT for 14 h. An aqueous solution of HCl (1N) was added and the resulting mixture was extracted with EtOAc, dried over MgSO4, filtered and evaporated to give an oil. This residue was taken up in CD3OD. The precipitate was filtered off and the mother liquids were evaporated and the resulting residue was then purified by chromatography (SiO2, gradient from 2/1 to 1/1 c-hex/EtOAc in about 30 min) to give the title product as a colorless oil (10 mg; 5.8%). M+(ESI): 459.0. HPLC (Condition A): Rt: 4.5 min (HPLC purity: 98.5%).

Workup

  1. customthe resulting reaction mixture
  2. extractionthe resulting mixture was extracted with EtOAc
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customto give an oil
  7. filtrationThe precipitate was filtered off
  8. customthe mother liquids were evaporated
  9. customthe resulting residue was then purified by chromatography (SiO2, gradient from 2/1 to 1/1 c-hex/EtOAc in about 30 min)

Sources & evidence

ORD record
ord-c77136028b8041f6b73a2e2d8d23f0ae
Source dataset
uspto-grants-2012_08
Patent number
US08247437B2

Reaction notes

Loading…