1-Methylpiperazine → HCID 66622181, compound

HRID 416375Notes

Reaction equation

HRID 416375 reaction equation
[Cl:1][C:2]1[C:33]([F:34])=[CH:32][CH:31]=[CH:30][C:3]=1[CH2:4][NH:5][C:6](=[O:29])[N:7]([CH:9]([CH2:25][CH2:26][CH:27]=O)[CH2:10][O:11][C:12](=[O:24])[NH:13][C:14]1[N:15]=[CH:16][C:17]2[C:22]([CH:23]=1)=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH3:8].[CH3:35][N:36]1[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.CC(O)=O.C(Cl)Cl>[Cl:1][C:2]1[C:33]([F:34])=[CH:32][CH:31]=[CH:30][C:3]=1[CH2:4][NH:5][C:6](=[O:29])[N:7]([CH:9]([CH2:25][CH2:26][CH2:27][N:39]1[CH2:40][CH2:41][N:36]([CH3:35])[CH2:37][CH2:38]1)[CH2:10][O:11][C:12](=[O:24])[NH:13][C:14]1[N:15]=[CH:16][C:17]2[C:22]([CH:23]=1)=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH3:8]

Participants

7

Reactant 3

HCID 531671-MethylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 76654753HCID 76654753, compound

Product 1

HCID 66622181HCID 66622181, compound

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolvent2×HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of isoquinolin-3-yl-carbamic acid 2-[3-(2-chloro-3-fluoro-benzyl)-1-methyl-ureido]-5-oxo-pentyl ester (2.37 g crude mixture, 4.92 mmol) in anhydrous DCE (5 mL) and AcOH 1 (1 mL) was added N-methyl piperazine (0.573 mL, 5.16 mmol) at RT After 3 h of stirring at RT, sodium triacetoxyborohydride (4.17 g, 19.7 mmol) was added in one portion followed by 10 mL DCE. The mixture was stirred for 2 h at RT, the diluted in CH2Cl2 and washed with aq. NaHCO3 and brine. After drying the solution over Na2SO4, the reaction mixture was concentrated and the resulting residue was purified on RP-HPLC using a mixture of acetonitrile and H2O with a TFA Buffer. The purified fractions were concentrated, redissolved in EtOAc and washed with saturated aq. NaHCO3. Removal of the solvent afforded isoquinolin-3-yl-carbamic acid 2-[3-(2-chloro-3-fluoro-benzyl)-1-methyl-ureido]-5-(4-methyl-piperazin-1-yl)-pentyl ester as the free base (1.43 g, 51%) LRMS (M+H+) m/z 571.3.

Workup

  1. stirringThe mixture was stirred for 2 h at RT
  2. washwashed with aq. NaHCO3 and brine
  3. dry with materialAfter drying the solution over Na2SO4
  4. concentrationthe reaction mixture was concentrated
  5. customthe resulting residue was purified on RP-HPLC
  6. additiona mixture of acetonitrile and H2O with a TFA Buffer
  7. concentrationThe purified fractions were concentrated
  8. dissolutionredissolved in EtOAc
  9. washwashed with saturated aq. NaHCO3
  10. customRemoval of the solvent

Sources & evidence

ORD record
ord-3262352cb53744e2be2f8986d2b4e514
Source dataset
uspto-grants-2012_01
Patent number
US08088793B2

Reaction notes

Loading…