Potassium Carbonate → 1-[2-Fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-5-isopropyl-6-(2,3,5-trimethyl-phenoxy)-1H-pyrimidine-2,4-dione

HRID 426261ノート

反応式

HRID 426261 の反応式
[CH:1]([C:4]1[C:5](=[O:21])[NH:6][C:7](=[O:20])[NH:8][C:9]=1[O:10][C:11]1[CH:16]=[C:15]([CH3:17])[CH:14]=[C:13]([CH3:18])[C:12]=1[CH3:19])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[F:28][C:29]1[CH:34]=[C:33]([CH2:35]OS(C)(=O)=O)[CH:32]=[C:31]([NH:41][CH2:42][C:43]2[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][CH:44]=2)[N:30]=1.[I-].[Li+]>CN(C=O)C.C(OCC)(=O)C>[F:28][C:29]1[CH:34]=[C:33]([CH2:35][N:8]2[C:9]([O:10][C:11]3[CH:16]=[C:15]([CH3:17])[CH:14]=[C:13]([CH3:18])[C:12]=3[CH3:19])=[C:4]([CH:1]([CH3:3])[CH3:2])[C:5](=[O:21])[NH:6][C:7]2=[O:20])[CH:32]=[C:31]([NH:41][CH2:42][C:43]2[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][CH:44]=2)[N:30]=1

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 66321Lithium iodideHCID 59184646Methanesulfonic acid 2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl esterHCID 591848065-Isopropyl-6-(2,3,5-trimethyl-phenoxy)-1H-pyrimidine-2,4-dione

生成物 1

HCID 591848531-[2-Fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-5-isopropyl-6-(2,3,5-trimethyl-phenoxy)-1H-pyrimidine-2,4-dione収率 42%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

5-Isopropyl-6-(2,3,5-trimethyl-phenoxy)-1H-pyrimidine-2,4-dione (39 mg, 0.135 mmol) was dissolved in 1.5 mL DMF. Potassium carbonate (31 mg, 2 eq.) was added and the reaction was stirred at room temperature for 10 minutes. Methanesulfonic acid 2-fluoro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl ester (0.135 mmol) and lithium iodide (15 mg, 1 eq.) were added. 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, 0-80% EtOAC/hexane) to give white powder (25 mg, 42%). LC-MS shows 533.1 (M+1). 1H NMR (300 MHz, CDCl3): δ 8.68 (b, 1H), 7.22 (d, 2H), 6.86 (d, 2H), 6.75 (s, 1H), 6.18 (s, 1H), 5.95 (d, 2H), 4.94 (d, 1H), 4.45 (d, 1H), 4.37 (s, 2H), 3.80 (s, 3H), 2.68 (m, 1H), 2.23 (s, 3H), 2.19 (s, 3H), 2.06 (s, 3H), 1.15 (dd, 6H).

後処理

  1. stirringThe reaction was stirred at room temperature overnight
  2. washby washing with brine
  3. concentrationThe organic layer was concentrated down
  4. custompurified (silica gel, 0-80% EtOAC/hexane)

出典と根拠

ORDレコード
ord-1ef665098f6c4832837b03d14e71cfd1
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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