Acetaldehyde → 2-(2-(2-(2-((4-(4-Ethylpiperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

HRID 1485173Notes

Reaction equation

HRID 1485173 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:19]=[C:18]([CH2:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[CH2:28][C:29]([NH2:31])=[O:30])[C:17]([C:32]([F:35])([F:34])[F:33])=[CH:16][N:15]=3)=[CH:9][CH:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH:36](=O)[CH3:37].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO.C(Cl)Cl>[CH2:36]([N:4]1[CH2:5][CH2:6][N:1]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:19]=[C:18]([CH2:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[CH2:28][C:29]([NH2:31])=[O:30])[C:17]([C:32]([F:33])([F:35])[F:34])=[CH:16][N:15]=3)=[CH:9][CH:8]=2)[CH2:2][CH2:3]1)[CH3:37]

Participants

6

Reactant 3

HCID 177AcetaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 601644802-(2-(2-(2-((4-(Piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

Product 1

HCID 601645892-(2-(2-(2-((4-(4-Ethylpiperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamideYield 76.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 2-(2-(2-(2-((4-(piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide (1) (0.020 g, 0.041 mmol) in anhydrous methanol (1.5 mL) were added acetaldehyde (0.0090 mL, 0.17 mmol) and sodium triacetoxyborohydride (0.044 g, 0.21 mmol) under an atmosphere of nitrogen The reaction was stirred at room temperature for 18 hours, the volatiles were removed in vacuo and the residue was diluted with EtOAc (15 mL) and sat. aq. NaHCO3 (10 mL). The layers were separated and the aqueous layer was extracted with EtOAc (10 mL), the combined organic layers were washed with water (10 mL), brine (10 mL), dried (MgSO4), filtered and concentrated in vacuo to give a solid which was taken up in DCM (˜10 mL) and methanol (˜1 mL) and concentrated in vacuo. The process was repeated with only DCM twice after which the sample was further dried on high-vacuum to give the title compound (10) (0.016 g, 76% yield) as an off-white solid; 1H NMR (400 MHz, d6-DMSO) δ 9.97 (s, 1H), 8.60 (s, 1H), 7.57 (d, J=8.9 Hz, 2H), 7.43 (s, 1H), 7.26-7.13 (m, 4H), 6.97-6.87 (m, 3H), 3.50 (s, 2H), 3.13-2.94 (m, 8H), 2.36 (q, J=7.2 Hz, 2H), 1.03 (t, J=7.2 Hz, 3H). 4 Aliphatic protons obscured by the residual DMSO. LCMS Method C: rt 4.82 min; m/z 513.3 [M+H]+.

Workup

  1. customthe volatiles were removed in vacuo
  2. additionthe residue was diluted with EtOAc (15 mL) and sat. aq. NaHCO3 (10 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (10 mL)
  5. washthe combined organic layers were washed with water (10 mL), brine (10 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a solid which
  10. concentrationmethanol (˜1 mL) and concentrated in vacuo
  11. customwas further dried on high-vacuum

Sources & evidence

ORD record
ord-25b4fe282ca64d25a15549c28fee2d73
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

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