Acetic Acid → HCID 70913292, compound

HRID 2208831Notes

Reaction equation

HRID 2208831 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:32](O)(=O)[CH3:33].C(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl.O>[CH2:1]([N:8]([CH2:32][CH3:33])[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

8

Reactant 5

HCID 176Acetic AcidHCID 177Acetaldehyde2×HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 70873880HCID 70873880, compound

Product 1

HCID 70913292HCID 70913292, compoundYield 36.1%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Procedure

To a solution of 3-(benzylamino)-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-2-(trifluoromethyl)benzamide (198 mg, 0.46 mmol) in DCE (5 ml) was added acetic acid (80 μl, 1.38 mmol) followed by acetaldehyde (129 μl, 2.31 mmol) after which the reaction was stirred at room temperature for 10 min. Then sodium triacetoxyborohydride (490 mg, 2.31 mmol) was added in one portion and the reaction was stirred at room temperature for 16 h. Further 4×130 uL treatments with acetaldehyde and 4×0.5 g sodium triacetoxyborohydride were performed over 3 days to completed the reaction. Water (100 ml) was then added to the reaction mixture and the aqueous phase was neutralized by the portionwise addition of NaHCO3. The aqueous phase was extracted with DCM (2×50 ml), then the combined organic phases 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 followed by purification via RP-HPLC to give the title compound as an off-white powder (76 mg, 34%). LC-MS 100%, m/z=458.3, 1H NMR (500 MHz, Chloroform-d) δ 11.70 (s, 1H), 7.42 (t, J=7.8 Hz, 1H), 7.36-7.27 (m, 5H), 7.24 (d, J=7.1 Hz, 1H), 7.12 (d, J=7.4 Hz, 1H), 7.03 (d, J=5.4 Hz, 1H), 5.90 (s, 1H), 4.50 (d, J=5.7 Hz, 2H), 4.05 (s, 2H), 2.96 (q, J=7.1 Hz, 2H), 2.36 (s, 3H), 2.15 (s, 3H), 0.89 (t, J=7.1 Hz, 3H).

Workup

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

Sources & evidence

ORD record
ord-406fbb36d6d64d3ca4fa0b9a74df5891
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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