Anisole → 5-(pyridin-3-yl)pyrimidine-2,4(1H,3H)-dione

HRID 1486554Notes

Reaction equation

HRID 1486554 reaction equation
C([N:14]1[CH:19]=[C:18]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)[C:17](=[O:26])[NH:16][C:15]1=[O:27])(C1C=CC=CC=1)C1C=CC=CC=1.C1(OC)C=CC=CC=1.OS(C(F)(F)F)(=O)=O.C(O)(C(F)(F)F)=O>>[N:22]1[CH:23]=[CH:24][CH:25]=[C:20]([C:18]2[C:17](=[O:26])[NH:16][C:15](=[O:27])[NH:14][CH:19]=2)[CH:21]=1

Participants

4

Reactant 3

HCID 7519AnisoleHCID 18539426TfOH-TFAHCID 900184521-Benzhydryl-5-(3-pyridyl)pyrimidine-2,4-dione

Product 1

HCID 122449965-(pyridin-3-yl)pyrimidine-2,4(1H,3H)-dione

Conditions

Temperature
0 °C

Procedure

The title compound was obtained according to the procedure described for the synthesis of Example 14 (Step 3), starting from 1-benzhydryl-5-(3-pyridyl)pyrimidine-2,4-dione (0.085 g, 0.239 mmol). Herein, anisole (0.163 g, 1.5 mmol) was added together with the triflic acid/TFA mixture, and the orange reaction mixture was here stirred for 1 hr at 0° C. TFA was removed by a stream of nitrogen and remaining TFA removed by co-evaporating with diethyl ether (40 mL). Water (15 mL) and acetonitrile (15 mL) was added, solidified in a dry ice-acetone bath, and the crude title compound was obtained by lyophilization. The crude was purified by column chromatography using a Teledyne ISCO apparatus (Dichloromethane:20% methanol in dichloromethane 30:70) to afford the title compound as, a triflic salt (0.067 g, 81%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 7.91 (dd, J=6.2, 5.8 Hz, 1H), 8.07 (d, J=6.1 Hz, 1H), 8.60 (dt, J=8.2, 1.6 Hz, 1H), 8.72 (dd, J=5.4, 1.4 Hz, 1H), 9.06 (d, J=2.1 Hz, 1H), 11.55 (s, 1H), 11.58 (d, =5.5 Hz, 1H). MS (ESI) m/z: 190 [M-H]+.

Workup

  1. customdescribed for the synthesis of Example 14 (Step 3)
  2. customTFA was removed by a stream of nitrogen
  3. customremoved by co-evaporating with diethyl ether (40 mL)
  4. additionWater (15 mL) and acetonitrile (15 mL) was added
  5. customsolidified in a dry ice-acetone bath
  6. customthe crude title compound was obtained by lyophilization
  7. customThe crude was purified by column chromatography

Sources & evidence

ORD record
ord-b598295493b04bc9959bacf7b0a39144
Source dataset
uspto-grants-2016_08
Patent number
US09428465B2

Reaction notes

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