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 426216ノート

反応式

HRID 426216 の反応式
[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

参加物

6

反応物 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

生成物 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)-acrylonitrile収率 70%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a stirred solution of 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 (335 mg, 0.611 mmol) and diethyl cyanomethyl-phosphonate (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).

後処理

  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))

出典と根拠

ORDレコード
ord-4e38fdae4ccc42ffb4489afb69faf27c
出典データセット
uspto-grants-2012_01
特許番号
US08106064B2

反応ノート

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