Methyl iodide → HCID 67958463, compound

HRID 1529413Notes

Reaction equation

HRID 1529413 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:17][CH2:16][C:13]2([CH2:15][CH2:14]2)[C@@H:12]([O:18][C:19]2[N:24]=[C:23]([C:25]3[C:33]4[C:28](=[CH:29][CH:30]=[C:31]([CH2:34][C:35]([O:37][CH:38]([CH3:40])[CH3:39])=[O:36])[CH:32]=4)[N:27]([C:41](OC(C)(C)C)=O)[N:26]=3)[CH:22]=[N:21][CH:20]=2)[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].I[CH3:49]>C1COCC1.CCOC(C)=O>[CH:38]([O:37][C:35](=[O:36])[CH:34]([C:31]1[CH:32]=[C:33]2[C:28](=[CH:29][CH:30]=1)[N:27]([CH3:41])[N:26]=[C:25]2[C:23]1[N:24]=[C:19]([O:18][C@H:12]2[CH2:11][N:10]([C:8]([O:7][C:3]([CH3:5])([CH3:4])[CH3:6])=[O:9])[CH2:17][CH2:16][C:13]32[CH2:14][CH2:15]3)[CH:20]=[N:21][CH:22]=1)[CH3:49])([CH3:39])[CH3:40]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 67959810HCID 67959810, compound

Product 1

HCID 67958463HCID 67958463, compoundYield 85.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

NaH in mineral oil (7.72 mg, 0.193 mmol) was added to a solution of (R)-tert-butyl 3-(6-((6-(tert-butoxycarbonyl)-6-azaspiro[2.5]octan-4-yl)oxy)pyrazin-2-yl)-5-(2-isopropoxy-2-oxoethyl)-1H-indazole-1-carboxylate (40 mg, 0.064 mmol) in THF (643 μl) at 0° C.; this was stirred for 15 min before iodomethane (12.04 μl, 0.193 mmol) was added. After 1 h at 0° C.; the mixture was warmed to RT and stirred for 1.5 h. The mixture was diluted with EtOAc (100 ml), added to a separatory funnel, and washed with saturated aqueous NH4Cl (2×75 ml) before the organic layer was separated, dried over Na2SO4, and concentrated. The crude was adsorbed onto silica and was purified via automated flash chromatography (silica gel) with 100% DCM to 4% MeOH/DCM to give (4R)-tert-butyl 4-((6-(5-(1-isopropoxy-1-oxopropan-2-yl)-1-methyl-1H-indazol-3-yl)pyrazin-2-yl)oxy)-6-azaspiro[2.5]octane-6-carboxylate (30 mg, 0.055 mmol, 85% yield) as a yellow oil. MS (ESI, pos. ion) m/z: 550.0 (M+1).

Workup

  1. additionwas added
  2. additionadded to a separatory funnel
  3. washwashed with saturated aqueous NH4Cl (2×75 ml) before the organic layer
  4. customwas separated
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customwas purified

Sources & evidence

ORD record
ord-62e8df8ffa1a4065a601478254a0d125
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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