Acetaldehyde → HCID 86594621, compound

HRID 915377Notes

Reaction equation

HRID 915377 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([C:13]3[N:14]([CH2:25][C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=4[F:33])[C:15](=[O:24])[C:16]4[C:21]([CH:22]=3)=[CH:20][CH:19]=[CH:18][C:17]=4[Cl:23])=[CH:10][CH:9]=2)=[CH:4][C:3]=1[C:34]([F:37])([F:36])[F:35].[CH:38](=O)[CH3:39]>C1(C)C=CC=CC=1.C(O)(=O)C>[Cl:23][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]2[C:16]=1[C:15](=[O:24])[N:14]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=1[F:33])[C:13]([C:11]1[S:12][C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][CH2:38][CH3:39])=[C:3]([C:34]([F:37])([F:36])[F:35])[CH:4]=3)=[CH:9][CH:10]=1)=[CH:22]2

Participants

5

Reactant 2

HCID 177AcetaldehydeHCID 86594622HCID 86594622, compound

Product 1

HCID 86594621HCID 86594621, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 1140TolueneSolvent

Procedure

To a solution of 3-[5-(4-amino-3-trifluoromethylphenyl)thiophen-2-yl]-8-chloro-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one (28 mg, 51 μmol) in toluene (1 mL) was added one drop of acetic acid, and a molar excess of acetaldehyde. The mixture was stirred for 20 minutes at ambient temperature and then concentrated under reduced pressure. The residue was taken up in 25% HOAc/MeOH (1 mL), and a molar excess of NaCNBH3 was added. After stirring for 16 hours at ambient temperature there was still starting material present. Additional acetaldehyde was added. After 30 minutes a yellow solid appeared in the reaction. This solid was collected by filtration and was purified by silica gel column chromatography eluting with a gradient from 0% to 20% ethyl acetate/hexane on silica. The product peak was collected to afford 8-chloro-2-(2,4-difluorobenzyl)-3-[5-(4-ethylamino-3-trifluoromethylphenyl)thiophen-2-yl]-2H-isoquinolin-1-one (10 mg, 34% yield) as a yellow solid. 1H-NMR (400 MHz, CDCl3): δ 7.62-7.60 (1H, m), 7.55-7.51 (3H, m), 7.44-7.40 (1H, m), 7.05-6.98 (2H, m), 6.85 (1H, d, J=3.8 Hz), 6.82-6.72 (3H, m), 6.67 (1H, s), 5.36 (2H, s), 4.40 (1H, s), 3.29-3.22 (2H, m), 1.32 (3H, t, J=7.1 Hz) ppm.

Workup

  1. concentrationconcentrated under reduced pressure
  2. additiona molar excess of NaCNBH3 was added
  3. stirringAfter stirring for 16 hours at ambient temperature
  4. additionAdditional acetaldehyde was added
  5. customAfter 30 minutes a yellow solid appeared in the reaction
  6. filtrationThis solid was collected by filtration
  7. customwas purified by silica gel column chromatography
  8. washeluting with a gradient from 0% to 20% ethyl acetate/hexane on silica
  9. customThe product peak was collected

Sources & evidence

ORD record
ord-e4c42b25f2474e108c43a4ba7807e391
Source dataset
uspto-grants-2007_09
Patent number
US07265131B2

Reaction notes

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