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

HRID 426215Notes

Reaction equation

HRID 426215 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][N:9]2[C:14]([O:15][C:16]3[CH:21]=[C:20]([CH3:22])[CH:19]=[C:18]([CH:23]4OCC[O:24]4)[CH:17]=3)=[C:13]([CH:28]([CH3:30])[CH3:29])[C:12](=[O:31])[NH:11][C:10]2=[O:32])[CH:5]=[C:4]([NH:33][CH2:34][C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=2)[N:3]=1.CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1>O.CC(C)=O>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][N:9]2[C:14]([O:15][C:16]3[CH:17]=[C:18]([CH:19]=[C:20]([CH3:22])[CH:21]=3)[CH:23]=[O:24])=[C:13]([CH:28]([CH3:29])[CH3:30])[C:12](=[O:31])[NH:11][C:10]2=[O:32])[CH:5]=[C:4]([NH:33][CH2:34][C:35]2[CH:36]=[CH:37][C:38]([O:41][CH3:42])=[CH:39][CH:40]=2)[N:3]=1

Participants

5

Reactant 2

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 591847941-[2-Chloro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-6-(3-[1,3]dioxolan-2-yl-5-methyl-phenoxy)-5-isopropyl-1H-pyrimidine-2,4-dione

Product 1

HCID 591847503-{3-[2-Chloro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yloxy}-5-methyl-benzaldehydeYield 50%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 180AcetoneSolvent

Procedure

A mixture of 1-[2-chloro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-6-(3-[1,3]dioxolan-2-yl-5-methyl-phenoxy)-5-isopropyl-1 H-pyrimidine-2,4-dione (908 mg, 1.53 mmol), PPTS (77 mg, 0.31 mmol), and water (7 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 (1:2)) to afford 350 mg (50%) of a white foam. 1H NMR (200 MHz, CDCl3) δ 1.11 (6H, d, J=6.8 Hz), 2.40 (3H, s), 2.68 (1H, m), 3.80 (3H, s), 4.29 (2H, d, J=5.4 Hz), 4.72 (2H, s), 5.02 (1H, t, J=5.4 Hz), 6.01 (1H, s), 6.26 (1H, s), 6.85-6.89 (3H, m), 7.09 (1H, s), 7.21-7.27 (2H, m), 7.40 (1H, s), 8.98 (1H, s), 9.89 (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 (1:2))

Sources & evidence

ORD record
ord-752138e75f764aa28d48074c5b101ade
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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