Trimethylsilyl iodide → 4-(((3S,4S)-4-ethylpyrrolidin-3-yl)amino)-6-(6-((2-methoxyacetamido)methyl)pyridin-3-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide, dihydroiodide

HRID 877782Notes

Reaction equation

HRID 877782 reaction equation
[C:1]([C:4]1[CH:9]=[N:8][N:7]2[CH:10]=[C:11]([C:13]3[CH:14]=[N:15][C:16]([CH2:19][NH:20][C:21](=[O:25])[CH2:22][O:23][CH3:24])=[CH:17][CH:18]=3)[CH:12]=[C:6]2[C:5]=1[NH:26][C@H:27]1[C@@H:31]([CH2:32][CH3:33])[CH2:30][N:29](C(OCC2C=CC=CC=2)=O)[CH2:28]1)(=[O:3])[NH2:2].[Si]([I:48])(C)(C)C>C(#N)C>[IH:48].[IH:48].[CH2:32]([C@H:31]1[CH2:30][NH:29][CH2:28][C@H:27]1[NH:26][C:5]1[C:6]2[N:7]([CH:10]=[C:11]([C:13]3[CH:14]=[N:15][C:16]([CH2:19][NH:20][C:21](=[O:25])[CH2:22][O:23][CH3:24])=[CH:17][CH:18]=3)[CH:12]=2)[N:8]=[CH:9][C:4]=1[C:1]([NH2:2])=[O:3])[CH3:33]

Participants

4

Reactant 2

HCID 85247Trimethylsilyl iodide2×HCID 68350395(3S,4S)-benzyl 3-((3-carbamoyl-6-(6-((2-methoxyacetamido)methyl)pyridin-3-yl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-4-ethylpyrrolidine-1-carboxylate

Product 1

HCID 1317326074-(((3S,4S)-4-ethylpyrrolidin-3-yl)amino)-6-(6-((2-methoxyacetamido)methyl)pyridin-3-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide, dihydroiodideYield 98%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of (3S,4S)-benzyl 3-((3-carbamoyl-6-(6-((2-methoxyacetamido)methyl)pyridin-3-yl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-4-ethylpyrrolidine-1-carboxylate (22 mg, 0.038 mmol) in Acetonitrile (1 mL) at 0° C. was added TMS-I (0.013 mL, 0.094 mmol) and after stirring 15 minutes at 0° C., the cooling bath was removed. At 3.5 hr, SM remained by HPLC. The reaction mixture was recooled to 0° C. and additional TMS-I (0.013 mL, 0.094 mmol) was added. After stirring 15 minutes at 0° C., the cooling bath was removed and the reaction mixture was stirred 2 hr at rt. The reaction mixture was recooled to 0° C. and 0.5 ml of MeOH was added. Stirring at 0° C. was continued for 30 minutes. At this time, the volatiles were removed in vacuo to afford crude 4-(((3S,4S)-4-ethylpyrrolidin-3-yl)amino)-6-(6-((2-methoxyacetamido)methyl)pyridin-3-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide, dihydroiodide (26 mg, 0.037 mmol, 98% yield) as a brown solid. The material was used as is in the next step.

Workup

  1. customthe cooling bath was removed
  2. waitAt 3.5 hr
  3. customwas recooled to 0° C.
  4. stirringAfter stirring 15 minutes at 0° C.
  5. customthe cooling bath was removed
  6. stirringthe reaction mixture was stirred 2 hr at rt
  7. customwas recooled to 0° C.
  8. addition0.5 ml of MeOH was added
  9. stirringStirring at 0° C.
  10. waitwas continued for 30 minutes
  11. customAt this time, the volatiles were removed in vacuo

Sources & evidence

ORD record
ord-4cb94e111a72452d9af46a9fafa6933f
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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