Hydrochloric Acid → HCID 57947598, compound

HRID 340900Notes

Reaction equation

HRID 340900 reaction equation
[Cl:1][C:2]1[C:36]([F:37])=[CH:35][CH:34]=[CH:33][C:3]=1[CH2:4][NH:5][C:6](=[O:32])[N:7]([C@H:9]([CH2:16][O:17][C:18](=[O:31])[NH:19][C:20]1[N:21]=[CH:22][C:23]2[C:28]([CH:29]=1)=[CH:27][C:26]([F:30])=[CH:25][CH:24]=2)[CH2:10][CH2:11][C:12]([O:14]C)=[O:13])[CH3:8].[Li+].[OH-].Cl>O1CCOCC1.CCOC(C)=O>[Cl:1][C:2]1[C:36]([F:37])=[CH:35][CH:34]=[CH:33][C:3]=1[CH2:4][NH:5][C:6](=[O:32])[N:7]([C@H:9]([CH2:16][O:17][C:18](=[O:31])[NH:19][C:20]1[N:21]=[CH:22][C:23]2[C:28]([CH:29]=1)=[CH:27][C:26]([F:30])=[CH:25][CH:24]=2)[CH2:10][CH2:11][C:12]([OH:14])=[O:13])[CH3:8]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 57947554HCID 57947554, compound

Product 1

HCID 57947598HCID 57947598, compoundYield 87.3%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (S)-methyl 4-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-(6-fluoroisoquinolin-3-ylcarbamoyloxy)pentanoate (400 mg, 0.748 mmol, 1.0 equiv.) in 1,4-dioxane (1 mL) was added LiOH (2 N, 1.5 mL, 2.99 mmol, 4.0 equiv.). The reaction mixture was stirred at RT for 1 h., then was acidified to pH 1-3 with HCl (1 N). The mixture was diluted in EtOAc. The organic layer was washed by H2O and brine, and concentrated. The resulting residue was purified on RP-HPLC using a mixture of acetonitrile and H2O to give (S)-4-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-(6-fluoroisoquinolin-3-ylcarbamoyloxy)pentanoic acid (340 mg, 87%). LRMS (M+H+) m/z 521.2.

Workup

  1. washThe organic layer was washed by H2O and brine
  2. concentrationconcentrated
  3. customThe resulting residue was purified on RP-HPLC
  4. additiona mixture of acetonitrile and H2O

Sources & evidence

ORD record
ord-2d68401e337e4a928354f03abb1a5ff1
Source dataset
uspto-grants-2014_11
Patent number
US08895582B2

Reaction notes

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