Formaldehyde → 2-(2-(2-(2-((4-(4-Methylpiperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

HRID 1473033Notes

Reaction equation

HRID 1473033 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.C=O.[C:38](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[CH3:38][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

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 601644802-(2-(2-(2-((4-(Piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

Product 1

HCID 601644812-(2-(2-(2-((4-(4-Methylpiperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamideYield 97%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a suspension of 2-(2-(2-(2-((4-(piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide (1) (0.015 g, 0.031 mmol) in anhydrous methanol (1.5 mL) were added a 37% aq. solution of formaldehyde (0.005 mL, 0.062 mmol) followed by sodium triacetoxyborohydride (0.033 g, 0.155 mmol) under an atmosphere of nitrogen. The reaction was stirred at room temperature for 1.5 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 (2×10 mL), the combined organic layers were washed with water (10 mL), brine (10 mL), dried (MgSO4), filtered and concentrated in vacuo to give the title compound (3) (14.5 mg, 97% yield) as a pale yellow solid; 1H NMR (400 MHz, d6-DMSO) δ 9.97 (s, 1H), 8.60 (s, 1H), 7.57 (d, J=9.0 Hz, 2H), 7.43 (s, 1H), 7.26-7.13 (m, 4H), 6.96-6.87 (m, 3H), 3.50 (s, 2H), 3.12-3.03 (m, 6H), 3.03-2.94 (m, 2H), 2.47-2.42 (m, 4H), 2.22 (s, 3H). LCMS Method C: rt 4.74 min; m/z 499.3 [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 (2×10 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

Sources & evidence

ORD record
ord-b4f00514c71341d2a5ba3147902b9e92
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

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