1,4-Dioxane hydrochloride → HCID 25164139, compound

HRID 416453Notes

Reaction equation

HRID 416453 reaction equation
[Cl:1][C:2]1[C:48]([F:49])=[CH:47][CH:46]=[CH:45][C:3]=1[CH2:4][NH:5][C:6](=[O:44])[N:7]([C@H:9]([CH2:27][O:28][C:29](=[O:43])[NH:30][C:31]1[O:35][N:34]=[C:33]([C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([F:42])[CH:37]=2)[CH:32]=1)[CH2:10][CH2:11][C:12]([N:14]1[CH2:19][CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16][CH2:15]1)=[O:13])[CH3:8].Cl.O1CCOCC1>CO>[F:42][C:38]1[CH:37]=[C:36]([C:33]2[CH:32]=[C:31]([NH:30][C:29](=[O:43])[O:28][CH2:27][C@@H:9]([N:7]([CH3:8])[C:6]([NH:5][CH2:4][C:3]3[CH:45]=[CH:46][CH:47]=[C:48]([F:49])[C:2]=3[Cl:1])=[O:44])[CH2:10][CH2:11][C:12](=[O:13])[N:14]3[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[O:35][N:34]=2)[CH:41]=[CH:40][CH:39]=1

Participants

4

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 57947939HCID 57947939, compound

Product 1

HCID 25164139HCID 25164139, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (S)-tert-butyl 4-(4-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-(3-(3-fluorophenyl)isoxazol-5-ylcarbamoyloxy)pentanoyl)piperazine-1-carboxylate (0.3 g, 0.36 mmol, 1.0 equiv.) in MeOH (2 mL) at 0° C., was added HCl/dioxane (4 N, 0.9 mL, 3.6 mmol, 10 equiv.). The solution was stirred at RT for 1 h. The solvents were removed and the residue was purified on RP-HPLC using a mixture of acetonitrile and H2O with 0.1% TFA. The elute was diluted with EtOAc (10 mL) and then basified with saturated NaHCO3. The organic layer was dried and concentrated to give (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-oxo-5-(piperazin-1-yl)pentyl 3-(3-fluorophenyl)isoxazol-5-ylcarbamate (0.2 g, 92%). LRMS (M+H+) m/z 605.1.

Workup

  1. customThe solvents were removed
  2. customthe residue was purified on RP-HPLC
  3. additiona mixture of acetonitrile and H2O with 0.1% TFA
  4. additionThe elute was diluted with EtOAc (10 mL)
  5. customThe organic layer was dried
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-c43ff47a54384ee584b0a69d16720ea6
Source dataset
uspto-grants-2012_01
Patent number
US08088793B2

Reaction notes

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