Diisopropylethylamine → (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-4-oxo-4-(pyrazin-2-ylmethylamino)butyl isoquinolin-3-ylcarbamate

HRID 409874Notes

Reaction equation

HRID 409874 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]([C@H:9]([CH2:14][O:15][C:16](=[O:28])[NH:17][C:18]1[N:19]=[CH:20][C:21]2[C:26]([CH:27]=1)=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:10][C:11]([OH:13])=O)[CH3:8].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:68][CH2:69][C:70]1[CH:75]=[N:74][CH:73]=[CH:72][N:71]=1>CCOC(C)=O.CN(C=O)C>[CH:20]1[C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:27]=[C:18]([NH:17][C:16](=[O:28])[O:15][CH2:14][C@@H:9]([N:7]([CH3:8])[C:6]([NH:5][CH2:4][C:3]2[CH:30]=[CH:31][CH:32]=[C:33]([F:34])[C:2]=2[Cl:1])=[O:29])[CH2:10][C:11](=[O:13])[NH:68][CH2:69][C:70]2[CH:75]=[N:74][CH:73]=[CH:72][N:71]=2)[N:19]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 266781(Pyrazin-2-yl)methanamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57947837(S)-3-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-4-(isoquinolin-3-ylcarbamoyloxy)butanoic acid

Product 1

HCID 57947597(S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-4-oxo-4-(pyrazin-2-ylmethylamino)butyl isoquinolin-3-ylcarbamateYield 76.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of the crude (S)-3-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-4-(isoquinolin-3-ylcarbamoyloxy)butanoic acid (1.47 mmol) and DMF (5 mL) were added DIEA (0.512 mL, 2.94 mmol) and HBTU (0.667 g, 1.76m mol). The resulting mixture was stirred at RT for 10 min and 2-aminomethyl pyrazine (0.192 g, 1.76 mmol) was added. The resulting mixture was stirred at RT for 30 min. The mixture was diluted with EtOAc (100 mL). The organic layer was washed by NaHCO3 solution and concentrated. The resulting residue was purified on silica gel column (DCM/MeOH) to give (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-4-oxo-4-(pyrazin-2-ylmethylamino)butyl isoquinolin-3-ylcarbamate (0.65 g, 76.2%). LRMS (M+H+) m/z 580.1

Workup

  1. stirringThe resulting mixture was stirred at RT for 30 min
  2. washThe organic layer was washed by NaHCO3 solution
  3. concentrationconcentrated
  4. customThe resulting residue was purified on silica gel column (DCM/MeOH)

Sources & evidence

ORD record
ord-74abafe99d96429ba02097adca3a23d9
Source dataset
uspto-grants-2014_06
Patent number
US08759374B2

Reaction notes

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