Trifluoroacetic acid → HCID 57947553, compound

HRID 340935Notes

Reaction equation

HRID 340935 reaction equation
[Cl:1][C:2]1[C:46]([F:47])=[CH:45][CH:44]=[CH:43][C:3]=1[CH2:4][NH:5][C:6](=[O:42])[N:7]([C@H:9]([CH2:27][O:28][C:29](=[O:41])[NH:30][C:31]1[N:32]=[CH:33][C:34]2[C:39]([CH:40]=1)=[CH:38][CH:37]=[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].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:33]1[C:34]2[C:39](=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:40]=[C:31]([NH:30][C:29](=[O:41])[O:28][CH2:27][C@@H:9]([N:7]([CH3:8])[C:6]([NH:5][CH2:4][C:3]2[CH:43]=[CH:44][CH:45]=[C:46]([F:47])[C:2]=2[Cl:1])=[O:42])[CH2:10][CH2:11][C:12](=[O:13])[N:14]2[CH2:15][CH2:16][NH:17][CH2:18][CH2:19]2)[N:32]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57947442HCID 57947442, compound

Product 1

HCID 57947553HCID 57947553, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-tert-butyl 4-(4-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-(isoquinolin-3-ylcarbamoyloxy)pentanoyl)piperazine-1-carboxylate (22 g, 32.8 mmol) in DCM (200 mL) was added TFA (100 mL). The reaction mixture was stirred at RT for 3 h and concentrated. The residue was purified on silica gel column using a mixture of MeOH and DCM. The fractions were concentrated, dissolved in water (200 mL), neutralized to pH 8-9 with 1N NaOH, and extracted with EtOAc (300 mL×3). The organic layer was dried over Na2SO4, filtered, and concentrated to give (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-oxo-5-(piperazin-1-yl)pentyl isoquinolin-3-ylcarbamate (14 g, 75%). LRMS (M+H) m/z 571.1.

Workup

  1. concentrationconcentrated
  2. customThe residue was purified on silica gel column
  3. additiona mixture of MeOH and DCM
  4. concentrationThe fractions were concentrated
  5. dissolutiondissolved in water (200 mL)
  6. extractionextracted with EtOAc (300 mL×3)
  7. dry with materialThe organic layer was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-ed55c5d6a3de4c0e89ce1f6d2004fa75
Source dataset
uspto-grants-2014_11
Patent number
US08895582B2

Reaction notes

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