Hydrochloric Acid → HCID 57947462, compound

HRID 409764Notes

Reaction equation

HRID 409764 reaction equation
[Cl:1][C:2]1[C:47]([F:48])=[CH:46][CH:45]=[CH:44][C:3]=1[CH2:4][NH:5][C:6](=[O:43])[N:7]([C@H:9]([CH2:27][O:28][C:29](=[O:42])[NH:30][C:31]1[N:32]=[CH:33][C:34]2[C:39]([CH:40]=1)=[CH:38][C:37]([F:41])=[CH:36][CH:35]=2)[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>CO>[F:41][C:37]1[CH:38]=[C:39]2[C:34](=[CH:35][CH:36]=1)[CH:33]=[N:32][C:31]([NH:30][C:29](=[O:42])[O:28][CH2:27][C@@H:9]([N:7]([CH3:8])[C:6]([NH:5][CH2:4][C:3]1[CH:44]=[CH:45][CH:46]=[C:47]([F:48])[C:2]=1[Cl:1])=[O:43])[CH2:10][CH2:11][C:12](=[O:13])[N:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)=[CH:40]2

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 57947909HCID 57947909, compound

Product 1

HCID 57947462HCID 57947462, compoundYield 73.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (S)-tert-butyl 4-(4-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-(6-fluoroisoquinolin-3-ylcarbamoyloxy)pentanoyl)piperazine-1-carboxylate (56 mg, 0.081 mmol, 1.0 equiv.) in MeOH (1 mL) was added HCl (4 M in 1,4-dioxane, 1 mL). The mixture was stirred overnight and concentrated. The resulting residue was purified on RP-HPLC using a mixture of acetonitrile and H2O. The fractions containing the product were combined and concentrated. The resulting solid was dissolved in EtOAc. The organic solution was washed with saturated NaHCO3. HCl (4 N) was added into the organic solution. The solution was then concentrated to give (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-oxo-5-(piperazin-1-yl)pentyl 6-fluoroisoquinolin-3-ylcarbamate (35 mg, 65%) as a HCl salt. LRMS (M+H+) m/z 589.2.

Workup

  1. concentrationconcentrated
  2. customThe resulting residue was purified on RP-HPLC
  3. additiona mixture of acetonitrile and H2O
  4. additionThe fractions containing the product
  5. concentrationconcentrated
  6. dissolutionThe resulting solid was dissolved in EtOAc
  7. washThe organic solution was washed with saturated NaHCO3
  8. additionHCl (4 N) was added into the organic solution
  9. concentrationThe solution was then concentrated

Sources & evidence

ORD record
ord-7761e4fc48fa40aaaeaa064586fc8b5b
Source dataset
uspto-grants-2014_06
Patent number
US08759374B2

Reaction notes

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