Methyl iodide → HCID 59605595, compound

HRID 1946172Notes

Reaction equation

HRID 1946172 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:15]2[N:16]([CH3:41])[C:17]3[C:22]([N:23]=2)=[C:21]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[N:20]=[C:19]([N:30]2[C:34]4[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=4[N:32]=[C:31]2[CH2:39][CH3:40])[N:18]=3)([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:45]>C1COCC1.C1OCCOCCOCCOCCOC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]([C:15]2[N:16]([CH3:41])[C:17]3[C:22]([N:23]=2)=[C:21]([N:24]2[CH2:25][CH2:26][O:27][CH2:28][CH2:29]2)[N:20]=[C:19]([N:30]2[C:34]4[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=4[N:32]=[C:31]2[CH2:39][CH3:40])[N:18]=3)([O:14][CH3:45])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59605258HCID 59605258, compound

Product 1

HCID 59605595HCID 59605595, compoundYield 69%

Reagents, catalysts & solvents 2

HCID 3633615-Crown-5CatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-[2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-4-hydroxypiperidine-1-carboxylic acid tert-butyl ester (1.3 g, 2.31 mmol) in THF (50 mL) was added NaH (112 mg, 2.80 mmol, 60% dispersion in mineral oil) and the resulting mixture allowed to stir for 5 min before the addition of iodomethane (175 μL, 2.80 mmol) and 15-Crown-5 (5 drops). The resulting mixture was stirred for 20 h quenched with H2O and extracted with 2-methyl THF. The organic phase was washed with brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 40-80%) affording 4-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-4-methoxypiperidine-1-carboxylic acid tert-butyl ester (915 mg, 69%). LCMS (method H): RT 3.40 min [M+H]+ 577.5

Workup

  1. customquenched with H2O
  2. extractionextracted with 2-methyl THF
  3. washThe organic phase was washed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 40-80%)

Sources & evidence

ORD record
ord-583c5f7028514c138d9f9d88cdff4862
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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