Trimethylsilyl iodide → 6-bromo-4-(((3S,4S)-4-methylpyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide

HRID 877761노트

반응식

HRID 877761 반응식
I[Si](C)(C)C.[Br:6][C:7]1[CH:8]=[C:9]2[C:14]([NH:15][C@H:16]3[C@@H:20]([CH3:21])[CH2:19][N:18](C(OCC4C=CC=CC=4)=O)[CH2:17]3)=[C:13]([C:32](=[O:34])[NH2:33])[CH:12]=[N:11][N:10]2[CH:35]=1.BrC1C=C2C(Cl)=C(C(N)=O)C=NN2C=1.N[C@H]1[C@@H](C)CN(C(OCC2C=CC=CC=2)=O)C1>C(#N)C>[Br:6][C:7]1[CH:8]=[C:9]2[C:14]([NH:15][C@H:16]3[C@@H:20]([CH3:21])[CH2:19][NH:18][CH2:17]3)=[C:13]([C:32]([NH2:33])=[O:34])[CH:12]=[N:11][N:10]2[CH:35]=1

참가 물질

6

반응물 4

HCID 85247Trimethylsilyl iodideHCID 682911926-Bromo-4-chloropyrrolo[1,2-b]pyridazine-3-carboxamideHCID 68350278(3S,4S)-benzyl 3-amino-4-methylpyrrolidine-1-carboxylateHCID 68350361(3S,4S)-benzyl 3-((6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-yl)amino)-4-methylpyrrolidine-1-carboxylate

생성물 1

HCID 682908116-bromo-4-(((3S,4S)-4-methylpyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

Iodotrimethylsilane (6.23 mL, 45.8 mmol) was added dropwise to a suspension of (3S,4S)-benzyl 3-((6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-yl)amino)-4-methylpyrrolidine-1-carboxylate (8.65 g, 18.31 mmol, prepared by coupling Intermediate 2 and enantiopure Intermediate 5 as previously described in Example 52) in acetonitrile (60 mL). The resulting mixture turned to a homogeneous solution several minutes after completion of addition and gradually turned to brown suspension. After 2 h at room temperature, the resulting mixture was quenched with methanol (10 mL), stirred for 5 min and concentrated in vacuo. The solid residue was diluted with ether (80 mL) and dichloromethane (80 mL), stirred for 30 min and filtered. The filter cake was washed with ether-dichloromethane (1:1 mixture, 160 mL), and dried under vacuum to give the desired 6-bromo-4-(((3S,4S)-4-methylpyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide as yellow powder, assumed as HI salt (10.64 g). 1H NMR (400 MHz, methanol-d4) δ ppm 8.20 (s, 1H), 7.73 (d, J=1.8 Hz, 1H), 7.03 (d, J=1.8 Hz, 1H), 5.03-4.92 (m, 1H), 3.83-3.72 (m, 1H), 3.67 (dd, J=12.0, 7.8 Hz, 1H), 3.49-3.40 (m, J=2.4 Hz, 1H), 3.14 (t, J=11.3 Hz, 1H), 2.85-2.71 (m, J=7.3 Hz, 1H), 1.25 (d, J=7.0 Hz, 3H); MS (ES+) m/z: 338.0 (M+H); LC retention time: 2.485 min (analytical HPLC Method H).

후처리

  1. customprepared
  2. customturned to a homogeneous solution several minutes
  3. additionafter completion of addition
  4. customthe resulting mixture was quenched with methanol (10 mL)
  5. concentrationconcentrated in vacuo
  6. additionThe solid residue was diluted with ether (80 mL) and dichloromethane (80 mL)
  7. stirringstirred for 30 min
  8. filtrationfiltered
  9. washThe filter cake was washed with ether-dichloromethane (1:1 mixture, 160 mL)
  10. customdried under vacuum

출처 및 근거

ORD 기록
ord-046249891d8040feb9b44029e07fd2c9
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08987268B2

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