Acetaldehyde → HCID 70874476, compound

HRID 2208830Notes

Reaction equation

HRID 2208830 reaction equation
[CH2:1]([NH:8][C:9]1[C:10]([C:28]([F:31])([F:30])[F:29])=[C:11]([CH:25]=[CH:26][CH:27]=1)[C:12]([NH:14][CH2:15][C:16]1[C:17](=[O:24])[NH:18][C:19]([CH3:23])=[CH:20][C:21]=1[CH3:22])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=O.[C:34](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)C.C([O-])(O)=O.[Na+]>ClCCCl.O.CC(O)=O>[CH2:1]([N:8]([CH3:34])[C:9]1[C:10]([C:28]([F:31])([F:29])[F:30])=[C:11]([CH:25]=[CH:26][CH:27]=1)[C:12]([NH:14][CH2:15][C:16]1[C:17](=[O:24])[NH:18][C:19]([CH3:23])=[CH:20][C:21]=1[CH3:22])=[O:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 177Acetaldehyde2×HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride3×HCID 70873880HCID 70873880, compound

Product 1

HCID 70874476HCID 70874476, compoundYield 23.5%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolvent2×HCID 962WaterSolvent

Procedure

To a solution of 3-(benzylamino)-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-2-(trifluoromethyl)benzamide (100 mg, 0.23 mmol) in DCE (5 ml) was added acetic acid (27 μl, 0.47 mmol) followed by paraformaldehyde (7 mg, 0.23 mmol) after which the reaction was stirred at room temperature for 10 min. Then sodium triacetoxyborohydride (74 mg, 0.35 mmol) was added in one portion and the reaction was stirred at room temperature for 16 h. Further treatment with acetaldehyde (35 mg), sodium triacetoxyborohydride (250 mg) and AcOH (100 ml) was performed. After a further 24 h further acetaldehyde (445 mg) and sodium triacetoxyborohydride (250 mg) were added and the reaction was stirred for a further 3 h. Water (20 ml) was then added to the reaction mixture and the aqueous phase was neutralised by the portionwise addition of NaHCO3. The aqueous phase was extracted with DCM (2×50 ml), then the combined organic phases were washed with brine, dried (Na2SO4) and evaporated. The product was purified using FCC over a 5 g Isolute, eluting with 0-5% MeOH in DCM to afford the title compound as an off-white powder (24 mg, 22%). LC-MS 95%, 4.12 min (7 minute LC-MS method), m/z=444.2, 1H NMR (500 MHz, Chloroform-d) δ 11.10 (br. s, 1H), 7.44 (t, J=7.8 Hz, 1H), 7.38-7.29 (m, 5H), 7.27-7.23 (m, 1H), 7.12 (d, J=7.4 Hz, 1H), 7.04 (t, J=5.6 Hz, 1H), 5.92 (s, 1H), 4.52 (d, J=5.9 Hz, 2H), 4.09 (s, 2H), 2.60 (s, 3H), 2.38 (s, 3H), 2.19 (s, 3H).

Workup

  1. stirringthe reaction was stirred at room temperature for 16 h
  2. stirringthe reaction was stirred for a further 3 h
  3. extractionThe aqueous phase was extracted with DCM (2×50 ml)
  4. washthe combined organic phases were washed with brine
  5. dry with materialdried (Na2SO4)
  6. customevaporated
  7. customThe product was purified
  8. washeluting with 0-5% MeOH in DCM

Sources & evidence

ORD record
ord-029ed315fab345bb9a539c378cfb091f
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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