Diethyl (cyanomethyl)phosphonate → 3-(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-phenyl)-acrylonitrile

HRID 426106Notes

Reaction equation

HRID 426106 reaction equation
[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:21]=[C:22]([CH3:24])[CH:23]=3)[CH:19]=O)=[C:13]([CH:25]([CH3:27])[CH3:26])[C:12](=[O:28])[NH:11][C:10]2=[O:29])[CH:5]=[C:4]([NH:30][CH2:31][C:32]2[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=2)[N:3]=1.[C:40]([CH2:42]P(=O)(OCC)OCC)#[N:41].CC(C)([O-])C.[K+]>C1COCC1.CC(=O)OCC>[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]=[CH:42][C:40]#[N:41])[CH:21]=[C:22]([CH3:24])[CH:23]=3)=[C:13]([CH:25]([CH3:27])[CH3:26])[C:12](=[O:28])[NH:11][C:10]2=[O:29])[CH:5]=[C:4]([NH:30][CH2:31][C:32]2[CH:33]=[CH:34][C:35]([O:38][CH3:39])=[CH:36][CH:37]=2)[N:3]=1

Participants

6

Reactant 3

HCID 75676Diethyl (cyanomethyl)phosphonateHCID 23665647Potassium tert-butoxideHCID 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-benzaldehyde

Product 1

HCID 866192293-(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-phenyl)-acrylonitrileYield 70%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of (16) (335 mg, 0.611 mmol) and diethyl cyanomethylphosphonate (104 μl, 0.64 mmol) in THF (10 ml) at 0° C. (ice bath) under nitrogen atmosphere, was added potassium t-butoxide (151 mg, 1.34 mmol). After stirring for 1 hr., the mixture was stirred for overnight at room temperature. The mixture was then diluted with EA, washed with aqueous saturated ammonium chloride solution, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was purified by silica gel column chromatography (eluent, EA:hexanes (1:2)) to afford 243 mg (70%) of a white foam; 1H NMR (200 MHz, CDCl3) δ 1.10 (6H, d, J=6.8 Hz), 2.32 (3H, s), 2.68 (1H, m), 3.78 (3H, s), 4.30 (2H, d, J=5.2 Hz), 4.68 (2H, s), 5.23 (1H, t, J=5.2 Hz), 5.82 (1H, d, J=16.6 Hz), 6.05 (1H, s), 6.21 (1H, s), 6.62 (2H, s), 6.84-6.90 (2H, m), 6.97 (1H, s), 7.18-7.27 (3H, m), 9.63 (1H, s).

Workup

  1. stirring, the mixture was stirred for overnight at room temperature
  2. washwashed with aqueous saturated ammonium chloride solution
  3. dry with materialdried with anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe residue was purified by silica gel column chromatography (eluent, EA:hexanes (1:2))

Sources & evidence

ORD record
ord-3792ad1e3e914803811e3c00348a84e0
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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