Formaldehyde → 3-(2-(2-((2-Methoxy-4-(1-methylpiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)benzamide

HRID 705758Notes

Reaction equation

HRID 705758 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH:6]=[CH:5][C:4]=1[NH:15][C:16]1[N:21]=[C:20]([CH2:22][CH2:23][C:24]2[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=2)[C:27]([NH2:29])=[O:28])[C:19]([C:33]([F:36])([F:35])[F:34])=[CH:18][N:17]=1.C=O.[C:39](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH:9]2[CH2:14][CH2:13][N:12]([CH3:39])[CH2:11][CH2:10]2)[CH:6]=[CH:5][C:4]=1[NH:15][C:16]1[N:21]=[C:20]([CH2:22][CH2:23][C:24]2[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=2)[C:27]([NH2:29])=[O:28])[C:19]([C:33]([F:34])([F:35])[F:36])=[CH:18][N:17]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 60162121HCID 60162121, compound

Product 1

HCID 601621223-(2-(2-((2-Methoxy-4-(1-methylpiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)benzamideYield 74.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 3-(2-(2-((2-methoxy-4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)benzamide (5) (0.021 g, 0.042 mmol) in anhydrous methanol (2.00 mL) was added 37% aqueous formaidehyde (0.012 mL, 0.16 mmol) and sodium triacetoxyborohydride (0.044 g, 0.21 mmol) under a N2 atmosphere. The mixture was then stirred for 1.5 hours. The resulting mixture was concentrated under reduced pressure and diluted with EtOAc (10 mL) and washed with sat. aqueous NaHCO3 (10 mL). The Aqueous was further extracted with EtOAc (10 mL) and the combined organic layers were washed with brine (10 mL) and water (10 mL) then dried using a phase separation cartridge. The organics were concentrated under reduced pressure and purified using silica gel column chromatography (0-30% MeOH/EtOAc+1% 2 M ethanolic NH3). The product was then taken up in minimal hot acetonitrile and water and freeze dried to give the title compound (6) (0.016 g, 74%) as a white solid; 1H NMR (400 MHz, d6-Acetone) δ 8.62 (s, 1H), 8.27 (dd, J=8.3, 4.1 Hz, 1H), 8.15 (s, 1H), 7.90 (s, 1H), 7.78 (d, J=7.5 Hz, 1H), 7.41 (m, 3H), 6.99 (d, J=1.7 Hz, 1H), 6.89 (dd, J=8.2, 1.6 Hz, 1H), 6.55 (s, 1H), 3.98 (s, 3H), 3.20 (m, 4H), 2.90 (m, 2H), 2.57 (m, 1H), 2.22 (s, 3H), 1.98 (td, J=11.2, 3.8 Hz, 2H), 1.78 (m, 4H). LCMS Method C: rt 4.97 min; m/z 514.2 [M+H]+.

Workup

  1. concentrationThe resulting mixture was concentrated under reduced pressure
  2. additiondiluted with EtOAc (10 mL)
  3. washwashed with sat. aqueous NaHCO3 (10 mL)
  4. extractionThe Aqueous was further extracted with EtOAc (10 mL)
  5. washthe combined organic layers were washed with brine (10 mL) and water (10 mL)
  6. customthen dried
  7. customa phase separation cartridge
  8. concentrationThe organics were concentrated under reduced pressure
  9. custompurified
  10. dry with materialwater and freeze dried

Sources & evidence

ORD record
ord-5ef9f58a93654499bf23f69693a4b4bf
Source dataset
uspto-grants-2015_11
Patent number
US09174946B2

Reaction notes

Loading…