Formaldehyde → HCID 178480187, compound

HRID 1853037Notes

Reaction equation

HRID 1853037 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[N:18]=[C:17]([OH:19])[N:16]4[CH:20]=[CH:21][N:22]=[C:15]4[CH:14]=3)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.C=O.[C:25](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>O1CCCC1.CN(C)C(=O)C.ClCCl>[CH3:25][N:1]1[CH2:2][CH2:3][CH:4]([C:7]2[CH:8]=[CH:9][C:10]([C:13]3[N:18]=[C:17]([OH:19])[N:16]4[CH:20]=[CH:21][N:22]=[C:15]4[CH:14]=3)=[CH:11][CH:12]=2)[CH2:5][CH2:6]1

Participants

8

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 1785174297-(4-(Piperidin-4-yl)phenyl)imidazo[1,2-c]pyrimidin-5-ol

Product 1

HCID 178480187HCID 178480187, compoundYield 86.6%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Procedure

To a suspension of 7-(4-(piperidin-4-yl)phenyl)imidazo[1,2-c]pyrimidin-5-ol (1.03 g, 3.50 mmol) in tetrahydrofuran (35 mL) and N,N-dimethylacetamide (2.5 mL) was added formaldehyde (5.21 mL, 70.0 mmol) followed by sodium triacetoxyborohydride (3.71 g, 17.5 mmol) and the reaction was allowed proceed at ambient temperature with stirring under nitrogen for 30 minutes. Aqueous saturated sodium bicarbonate was added slowly and gas evolution was observed. To the aqueous was added dichloromethane (100 mL) and a thick white precipitate was observed. The organic was collected and a second extraction with dichloromethane yielded a homogenous milky mixture. The biphasic mixture was filtered and the solid was washed with dichloromethane and retained. The biphasic mixture was separated and the aqueous was extracted with DCM. The organic layers were combined, dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting crude material was triturated with diethyl ether and the resulting solids were collected by means of vacuum filtration. The two crops of solids were combined to afford 7-(4-(1-methylpiperidin-4-yl)phenyl)imidazo[1,2-c]pyrimidin-5-ol (0.935 g, 3.03 mmol, 86.6% yield). MS (apci) m/z=309.2 (M+H).

Workup

  1. customwas allowed proceed at ambient temperature
  2. customThe organic was collected
  3. extractiona second extraction with dichloromethane
  4. customyielded a homogenous milky mixture
  5. filtrationThe biphasic mixture was filtered
  6. washthe solid was washed with dichloromethane
  7. customThe biphasic mixture was separated
  8. extractionthe aqueous was extracted with DCM
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe resulting crude material was triturated with diethyl ether
  13. filtrationthe resulting solids were collected by means of vacuum filtration

Sources & evidence

ORD record
ord-5067f2ae49b048b1b887a5ad770de58d
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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