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 426261노트

반응식

HRID 426261 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-1ef665098f6c4832837b03d14e71cfd1
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08106064B2

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