Diisopropylethylamine → (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-3-(2,2-difluoroethylamino)propyl isoquinolin-3-ylcarbamate

HRID 416430Notes

Reaction equation

HRID 416430 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:32])[O:13][CH2:14][C@@H:15]([N:18]([CH3:31])[C:19]([NH:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:24]=2[Cl:30])=[O:20])[CH2:16][NH2:17])[N:2]=1.FC(F)(F)S(O[CH2:39][CH:40]([F:42])[F:41])(=O)=O.CCN(C(C)C)C(C)C>C1COCC1>[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:32])[O:13][CH2:14][C@@H:15]([N:18]([CH3:31])[C:19]([NH:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:24]=2[Cl:30])=[O:20])[CH2:16][NH:17][CH2:39][CH:40]([F:42])[F:41])[N:2]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27740892,2-Difluoroethyl trifluoromethanesulfonateHCID 57947642(S)-3-amino-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)propyl isoquinolin-3-ylcarbamate

Product 1

HCID 57947556(S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-3-(2,2-difluoroethylamino)propyl isoquinolin-3-ylcarbamateYield 56.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-3-amino-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)propyl isoquinolin-3-ylcarbamate (200 mg, 0.44 mmol) in THF (2.0 mL) were added 2,2-difluoroethyl trifluoromethanesulfonate (94 mg, 0.44 mmol) and DIEA (0.15 mL, 0.88 mmol) at RT The reaction mixture was stirred at RT for 30 min. The solvent was removed. The resulting residue was dissolved in MeOH and mixture was purified on RP-HPLC using a mixture of acetonitrile and water to give (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-3-(2,2-difluoroethylamino)propyl isoquinolin-3-ylcarbamate (130 mg, 56% for two steps). LRMS (M+H+) m/z 524.2.

Workup

  1. customThe solvent was removed
  2. dissolutionThe resulting residue was dissolved in MeOH
  3. custommixture was purified on RP-HPLC
  4. additiona mixture of acetonitrile and water

Sources & evidence

ORD record
ord-01dc562fe03a4881878999ccb26d16b2
Source dataset
uspto-grants-2012_01
Patent number
US08088793B2

Reaction notes

Loading…