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 426256노트

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HRID 426256 반응식
[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

참가 물질

7

반응물 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

생성물 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-benzonitrile수율 34%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

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

출처 및 근거

ORD 기록
ord-fa8d926c66304df9b295e64d9ca65fb2
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08106064B2

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