Acetic Acid → HCID 66781514, compound

HRID 1095742Notes

Reaction equation

HRID 1095742 reaction equation
[F:1][C@H:2]1[C@H:7]([O:8][C:9]2[CH:10]=[CH:11][CH:12]=[C:13]3[C:18]=2[N:17]=[C:16]([C:19]2[N:23]4[CH:24]=[CH:25][C:26]([O:28][CH2:29][CH2:30][O:31][CH3:32])=[CH:27][C:22]4=[N:21][CH:20]=2)[CH:15]=[CH:14]3)[CH2:6][CH2:5][NH:4][CH2:3]1.C=O.[C:35](O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[F:1][C@H:2]1[C@H:7]([O:8][C:9]2[CH:10]=[CH:11][CH:12]=[C:13]3[C:18]=2[N:17]=[C:16]([C:19]2[N:23]4[CH:24]=[CH:25][C:26]([O:28][CH2:29][CH2:30][O:31][CH3:32])=[CH:27][C:22]4=[N:21][CH:20]=2)[CH:15]=[CH:14]3)[CH2:6][CH2:5][N:4]([CH3:35])[CH2:3]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 11430Potassium CarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 59176329HCID 59176329, compound

Product 1

HCID 66781514HCID 66781514, compoundYield 71.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 8-((trans)-3-fluoropiperidin-4-yloxy)-2-(7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinoline (Example 20; 185 mg, 0.42 mmol) in CH2Cl2 (5 mL) was added formaldehyde (316 μL, 37% in water, 4.2 mmol) followed by acetic acid (30 μL, 0.51 mmol) and sodium triacetoxyborohydride (270 mg, 1.27 mmol). The mixture was stirred vigorously at ambient temperature for 48 hours, then treated with 10% aq. K2CO3 (20 mL) and stirred for 10 minutes. The mixture was extracted with CH2Cl2, and the combined organic phases were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified via flash column chromatography using gradient elution (CH2Cl2 to 2% MeOH/CH2Cl2 to 5% MeOH/CH2Cl2) then dissolved in CHCl3 (5 mL) and treated with 4N HCl/dioxane (2 mL). After stirring for 20 minutes at ambient temperature the mixture was concentrated. The residue was triturated with ether, filtered and dried in vacuo to provide 136 mg (61%) of desired product as the di-HCl salt as a solid. MS APCI (+) m/z 451.2 (M+1) detected.

Workup

  1. stirringstirred for 10 minutes
  2. extractionThe mixture was extracted with CH2Cl2
  3. washthe combined organic phases were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified via flash column chromatography
  8. washelution (CH2Cl2 to 2% MeOH/CH2Cl2 to 5% MeOH/CH2Cl2)
  9. dissolutionthen dissolved in CHCl3 (5 mL)
  10. additiontreated with 4N HCl/dioxane (2 mL)
  11. stirringAfter stirring for 20 minutes at ambient temperature the mixture
  12. concentrationwas concentrated
  13. customThe residue was triturated with ether
  14. filtrationfiltered
  15. customdried in vacuo

Sources & evidence

ORD record
ord-9a2850d1300e4830aa9e4bcdc564fbff
Source dataset
uspto-grants-2012_03
Patent number
US08138181B2

Reaction notes

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