Acetic Acid → HCID 67515392, compound

HRID 1754354Notes

Reaction equation

HRID 1754354 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12](=[O:13])[C:11]([CH3:15])([CH3:14])[O:10][N:9]=2)=[CH:4][C:3]=1[C:16]1[CH:21]=[CH:20][C:19]([NH:22][C:23](=[O:32])[C:24]2[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=2[F:31])=[CH:18][CH:17]=1.C=O.[C:35]([BH3-])#N.[Na+].C(O)(=O)C>CO>[CH3:15][C:11]1([CH3:14])[O:10][N:9]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([NH:1][CH3:35])=[C:3]([C:16]3[CH:17]=[CH:18][C:19]([NH:22][C:23](=[O:32])[C:24]4[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=4[F:31])=[CH:20][CH:21]=3)[CH:4]=2)[C:12]1=[O:13]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 57330890HCID 57330890, compound

Product 1

HCID 67515392HCID 67515392, compoundYield 16.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a 0° C. solution of Example 134 (50 mg, 0.11 mmol, 1.0 eq) in methanol (5 mL) was added formaldehyde (37% aqueous solution) (10 μL, 0.12 mmol, 1.1 eq). After stirring for 30 min at room temperature, sodium cyanoborohydride (8 mg, 0.14 mmol, 1.2 eq) was added to the above reaction mixture followed by a catalytic amount of acetic acid. The resulting mixture was stirred at room temperature for 12 h. The solvent was removed under vacuum and the residue was dissolved in ethyl acetate (10 mL) and washed with water (5 mL), brine (5 mL), dried (Na2SO4) and filtered. The filtrate was evaporated under vacuum and the crude product was purified by column chromatography (silica gel, DCM:MeOH as eluent) to afford 8 mg of title compound 1HNMR (400 MHz, CDCl3) δ 8.07 (dd, J=8.5, 2.0 Hz, 1H), 7.87 (d, J=2.0 Hz, 1H), 7.45-7.09 (m, 3H), 7.46-7.43 (m, 3H), 7.04 (t, J=8.0 Hz, 2H), 6.72 (d, J=8.5 Hz, 1H), 4.33 (s, 1H, D2O exchangeable), 2.86 (s, 3H), 1.45 (s, 6H); ESI-MS (m/z) 450 (MH)+.

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 12 h
  2. customThe solvent was removed under vacuum
  3. dissolutionthe residue was dissolved in ethyl acetate (10 mL)
  4. washwashed with water (5 mL), brine (5 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customThe filtrate was evaporated under vacuum
  8. customthe crude product was purified by column chromatography (silica gel, DCM:MeOH as eluent)

Sources & evidence

ORD record
ord-2d876bae8b8c4f5d9e04f782d0d5390a
Source dataset
uspto-grants-2015_10
Patent number
US09169242B2

Reaction notes

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