Formaldehyde → HCID 59395953, compound

HRID 1192284Notes

Reaction equation

HRID 1192284 reaction equation
[CH3:1][NH:2][C@H:3]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]=[CH:14][N:13]=2)[CH2:8][CH2:7]1)=[O:5].C=O.[BH-](OC(C)=O)(OC(C)=O)O[C:33](C)=O.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[CH3:1][N:2]([C@H:3]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:4]([N:6]1[CH2:7][CH2:8][N:9]([C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]=[CH:14][N:13]=2)[CH2:10][CH2:11]1)=[O:5])[CH3:33]

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 59395929HCID 59395929, compound

Product 1

HCID 59395953HCID 59395953, compoundYield 48.6%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of (2R)-2-(N-Methylamino)-3-phenyl-1-(4-quinazolin-4-yl-piperazin-1-yl)-propan-1-one (free-base, 14 mg, 0.037 mmol) in 1,2-dichloroethane was added a solution of formaldehyde (37% w/w, 50 μL, 0.61 mmol) and then Na(OAc)3BH (0.12 mmol). The reaction mixture was stirred at room temperature for 3 hours, after which saturated NaHCO3 was added, and the reaction mixture was stirred 10 minutes. The suspension was extracted with DCM, and the combined extracts were dried (Na2SO4), filtered, and concentrated by rotary evaporation. The residue was filtered through a Fluorosil plug with ETOAC, and the filtrate was concentrated by rotary evaporation. The resulting residue was dissolved in ether and excess 4M HCl/dioxane was added. The yellow solids were isolated by filtration with nitrogen pressure and dried under reduced pressure to afford the desired product (7 mg, 41%) as the dihydrochloride salt. Rt 2.20. MS (ESI+) [M+H]+ 390.

Workup

  1. stirringthe reaction mixture was stirred 10 minutes
  2. extractionThe suspension was extracted with DCM
  3. dry with materialthe combined extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated by rotary evaporation
  6. filtrationThe residue was filtered through a Fluorosil plug with ETOAC
  7. concentrationthe filtrate was concentrated by rotary evaporation
  8. dissolutionThe resulting residue was dissolved in ether
  9. additionexcess 4M HCl/dioxane was added
  10. customThe yellow solids were isolated by filtration with nitrogen pressure
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-5cd7b2fb76c54032aba4f60f2c4c7a4d
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

Loading…