Potassium Carbonate → 3-{5-Cyclopropyl-3-[2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl}-5-methyl-benzonitrile

HRID 426256ノート

反応式

HRID 426256 の反応式
[CH:1]1([C:4]2[C:9](=[O:10])[NH:8][C:7](=[O:11])[N:6]([CH2:12][C:13]3[CH:18]=[C:17]([F:19])[N:16]=[C:15](F)[CH:14]=3)[C:5]=2[C:21]([C:23]2[CH:24]=[C:25]([CH:28]=[C:29]([CH3:31])[CH:30]=2)[C:26]#[N:27])=[O:22])[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].FC1C=C(COS(C)(=O)=O)C=C([NH:51][CH2:52][C:53]2[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[CH:55][CH:54]=2)N=1.[I-].[Li+]>CN(C=O)C.C(OCC)(=O)C>[CH:1]1([C:4]2[C:9](=[O:10])[NH:8][C:7](=[O:11])[N:6]([CH2:12][C:13]3[CH:14]=[C:15]([NH:51][CH2:52][C:53]4[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[CH:55][CH:54]=4)[N:16]=[C:17]([F:19])[CH:18]=3)[C:5]=2[C:21]([C:23]2[CH:24]=[C:25]([CH:28]=[C:29]([CH3:31])[CH:30]=2)[C:26]#[N:27])=[O:22])[CH2:2][CH2:3]1

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 66321Lithium iodideHCID 250296833-[5-Cyclopropyl-3-(2,6-difluoro-pyridin-4-ylmethyl)-2,6-dioxo 1,2,3,6tetrahydro-pyrimidine-4-carbonyl]-5-methyl-benzonitrileHCID 59184646Methanesulfonic acid 2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl ester

生成物 1

HCID 591847693-{5-Cyclopropyl-3-[2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl}-5-methyl-benzonitrile収率 34%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

3-[5-Cyclopropyl-3-(2,6-difluoro-pyridin-4-ylmethyl)-2,6-dioxo-1,2,3,6tetrahydro-pyrimidine-4-carbonyl]-5-methyl-benzonitrile (16 mg, 0.054 mmol) was dissolved in 0.5 mL DMF. Potassium carbonate (7.5 mg, 1 eq.) and methanesulfonic acid 2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl ester (1 eq.) were added to the reaction, followed by lithium iodide (7.2 mg, 1 eq.) The reaction was stirred at room temperature overnight. Ethyl acetate was added to the reaction mixture, followed by washing with brine. The organic layer was concentrated down and purified (silica gel, 20-80% EtOAc/hexane) to give light yellow oil (10 mg, 34%). LC-MS shows 540.0 (M+1). 1H NMR (300 MHz, CDCl3): δ 7.81 (s, 1H), 7.63 (s, 1H), 7.59 (s, 1H), 7.23 (s, 1H), 7.21 (s, 2H), 6.91 (s, 1H), 6.88 (s, 1H), 5.80 (s, 1H), 5.78 (s, 1H), 4.26 (d, 2H), 3.80 (s, 2H), 2.39 (s, 3H), 0.9 (m, 1H), 0.62 (m, 3H), 0.41 (m, 1H).

後処理

  1. washby washing with brine
  2. concentrationThe organic layer was concentrated down
  3. custompurified (silica gel, 20-80% EtOAc/hexane)

出典と根拠

ORDレコード
ord-fa8d926c66304df9b295e64d9ca65fb2
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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