Iodoethane → HCID 86717959, compound

HRID 2275881Notes

Reaction equation

HRID 2275881 reaction equation
[CH:1]12[NH:9][CH:5]([CH2:6][CH2:7][CH2:8]1)[CH2:4][CH:3]([NH:10][C:11]([C:13]1[N:17]3[CH:18]=[CH:19][CH:20]=[C:21]([O:22][CH2:23][C:24]4[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=4[F:31])[C:16]3=[N:15][C:14]=1[CH3:32])=[O:12])[CH2:2]2.[CH2:33]1COC[CH2:34]1.[H-].[Na+].ICC>C(OCC)(=O)C>[F:30][C:29]1[CH:28]=[CH:27][CH:26]=[C:25]([F:31])[C:24]=1[CH2:23][O:22][C:21]1[C:16]2[N:17]([C:13]([C:11]([NH:10][CH:3]3[CH2:2][CH:1]4[N:9]([CH2:33][CH3:34])[CH:5]([CH2:6][CH2:7][CH2:8]4)[CH2:4]3)=[O:12])=[C:14]([CH3:32])[N:15]=2)[CH:18]=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 6340IodoethaneHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 86717960HCID 86717960, compound

Product 1

HCID 86717959HCID 86717959, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

60 mg of N-(9-azabicyclo[3.3.1]non-3-yl)-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]-pyridine-3-carboxamide (Example 27, 0.14 mmol) were initially charged in 1.4 ml of abs. THF, 4.2 mg of sodium hydride (purity 95%, 0.16 mmol) were added and the mixture was stirred at RT for 15 min. 0.011 ml of iodoethane (0.14 mmol) were then added dropwise, and the mixture was stirred at RT overnight. The reaction mixture was diluted with ethyl acetate and washed twice with water. The organic phase was washed with saturated aqueous sodium chloride solution, dried over sodium sulphate and filtered. The filtrate was concentrated and dried. The crude product was purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). The product-containing fractions were concentrated and the residue taken up in ethyl acetate and washed with saturated aqueous sodium bicarbonate solution. The organic phase was dried over sodium sulphate and filtered and the filtrate was concentrated and lyophilized. This gave 35 mg of the title compound (55% of theory).

Workup

  1. stirringthe mixture was stirred at RT overnight
  2. washwashed twice with water
  3. washThe organic phase was washed with saturated aqueous sodium chloride solution
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated
  7. customdried
  8. customThe crude product was purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA)
  9. concentrationThe product-containing fractions were concentrated
  10. washwashed with saturated aqueous sodium bicarbonate solution
  11. dry with materialThe organic phase was dried over sodium sulphate
  12. filtrationfiltered
  13. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-ffa35c36ecdf4311bb5f59086b62c318
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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