Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1) → 3-{3-[2-Fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yloxy}-5-methyl-benzaldehyde

HRID 426212Notes

Reaction equation

HRID 426212 reaction equation
[O:1]1CCO[CH:2]1[C:6]1[CH:7]=[C:8]([CH:39]=[C:40]([CH3:42])[CH:41]=1)[O:9][C:10]1[N:15]([CH2:16][C:17]2[CH:22]=[C:21]([NH:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)[N:20]=[C:19]([F:33])[CH:18]=2)[C:14](=[O:34])[NH:13][C:12](=[O:35])[C:11]=1[CH:36]([CH3:38])[CH3:37].CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1>O.CC(C)=O>[F:33][C:19]1[CH:18]=[C:17]([CH2:16][N:15]2[C:10]([O:9][C:8]3[CH:7]=[C:6]([CH:41]=[C:40]([CH3:42])[CH:39]=3)[CH:2]=[O:1])=[C:11]([CH:36]([CH3:37])[CH3:38])[C:12](=[O:35])[NH:13][C:14]2=[O:34])[CH:22]=[C:21]([NH:23][CH2:24][C:25]2[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=2)[N:20]=1

Participants

5

Reactant 2

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 591847436-(3-[1,3]Dioxolan-2-yl-5-methyl-phenoxy)-1-[2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-5-isopropyl-1H-pyrimidine-2,4-dione

Product 1

HCID 591848683-{3-[2-Fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yloxy}-5-methyl-benzaldehydeYield 83%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 180AcetoneSolvent

Procedure

A mixture of 6-(3-[1,3]dioxolan-2-yl-5-methyl-phenoxy)-1-[2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-5-isopropyl-1H-pyrimidine-2,4-dione (714 mg, 1.24 mmol), PPTS (62 mg, 0.25 mmol), and water (5 drops) in acetone (10 ml) was heated under reflux for 3 hr. After cooling to room temperature, the mixture was evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, EA: hexanes (from 1:1 to 2:3)) to afford 548 mg (83%) of a white solid. 1H NMR (200 MHz, CD3OD/CDCl3) δ 1.00 (6H, d, J=7.4 Hz), 2.30 (3H, s), 2.58 (1H, m), 3.71 (3H, s), 4.19 (2H, s), 4.65 (2H, s), 5.78 (1H, s), 5.86 (1H, s), 6.76-6.80 (3H, m), 7.02 (1H, s), 7.11-7.16 (2H, s), 7.32 (1H, s), 9.78 (1H, s).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 3 hr
  3. customthe mixture was evaporated in vacuo
  4. customthe residue was purified by silica gel column chromatography (eluent, EA: hexanes (from 1:1 to 2:3))

Sources & evidence

ORD record
ord-326889ba091446b3803674c06f54ab91
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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