Acetone → HCID 57947800, compound

HRID 416366Notes

Reaction equation

HRID 416366 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([NH:11][C:12](=[O:40])[O:13][CH2:14][C@@H:15]([N:26]([CH3:39])[C:27]([NH:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[C:32]=2[Cl:38])=[O:28])[CH2:16][CH2:17][C:18](=[O:25])[N:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[N:2]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[CH3:55][C:56]([CH3:58])=O>C(Cl)Cl.C(O)(=O)C>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([NH:11][C:12](=[O:40])[O:13][CH2:14][C@@H:15]([N:26]([CH3:39])[C:27]([NH:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[C:32]=2[Cl:38])=[O:28])[CH2:16][CH2:17][C:18]([N:19]2[CH2:20][CH2:21][N:22]([CH:56]([CH3:58])[CH3:55])[CH2:23][CH2:24]2)=[O:25])[N:2]=1

Participants

6

Reactant 3

HCID 180AcetoneHCID 5049666Sodium triacetoxyborohydrideHCID 57947553HCID 57947553, compound

Product 1

HCID 57947800HCID 57947800, compoundYield 82%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-oxo-5-(piperazin-1-yl)pentyl isoquinolin-3-ylcarbamate (610 mg, 1.07 mmol) in acetone (1 mL) and DCM (1 mL) was added acetic acid (4 drops, ˜0.2 mL). The reaction mixture was stirred at RT for 30 min. To this mixture was added solid NaBH(OAc)3 and the resulting mixture was stirred at RT for 1 h and concentrated. The residue was purified on RP-HPLC using a mixture of acetonitrle and water (0.1% HCOOH buffer). The fractions was collected, concentrated to dryness, and re-dissolved in EtOAc. The organic mixture was washed with Na2CO3, dried over Na2SO4, filtered, and concentrated to give (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-(4-isopropylpiperazin-1-yl)-5-oxopentyl isoquinolin-3-ylcarbamate (540 mg, 82%) as white solid. LRMS (M+H+) m/z 613.3.

Workup

  1. stirringthe resulting mixture was stirred at RT for 1 h
  2. concentrationconcentrated
  3. customThe residue was purified on RP-HPLC
  4. additiona mixture of acetonitrle and water (0.1% HCOOH buffer)
  5. customThe fractions was collected
  6. concentrationconcentrated to dryness
  7. dissolutionre-dissolved in EtOAc
  8. washThe organic mixture was washed with Na2CO3
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-231144f54352401aae9a40db0a72bd6e
Source dataset
uspto-grants-2012_01
Patent number
US08088793B2

Reaction notes

Loading…