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

HRID 416445노트

반응식

HRID 416445 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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, 1.76 mmol). The resulting mixture was stirred at RT for 10 min and 2-aminomethylpyrazine (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

후처리

  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)

출처 및 근거

ORD 기록
ord-e8e2177357734c7bbad86a92b1dcfaef
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08088793B2

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