Methyl iodide → HCID 86696462, compound

HRID 870755Notes

Reaction equation

HRID 870755 reaction equation
[Br:1][C:2]1[N:6]2[N:7]=[C:8]([NH:11][CH2:12][C@@H:13]3[CH2:17][CH2:16][CH2:15][N:14]3[C:18](=[O:23])[CH2:19][CH:20]([CH3:22])[CH3:21])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[H-].[Na+].[CH3:26]I.[Cl-].[NH4+]>C1COCC1>[Br:1][C:2]1[N:6]2[N:7]=[C:8]([N:11]([CH2:12][C@@H:13]3[CH2:17][CH2:16][CH2:15][N:14]3[C:18](=[O:23])[CH2:19][CH:20]([CH3:21])[CH3:22])[CH3:26])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 86696463HCID 86696463, compound

Product 1

HCID 86696462HCID 86696462, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-1-(2-(((3-bromoimidazo[1,2-b]pyridazin-6-yl)amino)methyl)pyrrolidin-1-yl)-3-methylbutan-1-one (380 mg, 1.0 mmol) in THF (10 mL) was added sodium hydride (120 mg, 3.0 mmol) at rt. After stirring for 15 min, methyl iodide was added dropwise. The reaction was stirred at it for overnight and worked up with ammonium chloride solution, extracted with ethyl acetate, concentrated and purified by ISCO column chromatography (10% MeOH/DCM) to give non-pure product. It was further purified by Prep HPLC (neutral) to give (S)-1-(2-(((3-bromoimidazo[1,2-b]pyridazin-6-yl)(methyl)amino)methyl)pyrrolidin-1-yl)-3-methylbutan-1-one as oil. 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.65-7.75 (m, 1H), 7.44-7.52 (m, 1H), 7.04-7.22 (m, 1H), 4.45-4.61 (m, 1H), 3.45-3.92 (m, 4H), 3.19-3.23 (m, 3H), 1.90-2.32 (m, 7H), 0.78-0.92 (m, 6H); LRMS (ESI) m/e 394.1 [(M+H)+, calcd for C17H25BrN5O 395.3].

Workup

  1. stirringThe reaction was stirred at it for overnight
  2. extractionextracted with ethyl acetate
  3. concentrationconcentrated
  4. custompurified by ISCO column chromatography (10% MeOH/DCM)
  5. customto give non-pure product
  6. customIt was further purified by Prep HPLC (neutral)

Sources & evidence

ORD record
ord-d3b7e834866c40a188a0dbfcfb068524
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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