N,N-Dimethylglycine → 5-(4-chlorobenzyl)-3-(3-hydroxypropyl)-1-methyl-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 60448

반응식

HRID 60448 반응식
C([O:3][CH2:4][CH2:5][CH2:6][N:7]1[C:12](=[O:13])[C:11]2[C:14]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)=[C:15](Br)[CH:16]=[N:17][C:10]=2[N:9]([CH3:27])[C:8]1=[O:28])=O.CN(C)CC(O)=O.C([O-])([O-])=O.[Cs+].[Cs+].[F:42][C:43]([F:53])([F:52])[O:44][C:45]1[CH:46]=[C:47]([OH:51])[CH:48]=[CH:49][CH:50]=1>O1CCOCC1.CC(=O)OCC.O.[Cu]I>[Cl:26][C:23]1[CH:22]=[CH:21][C:20]([CH2:19][C:14]2[C:11]3[C:12](=[O:13])[N:7]([CH2:6][CH2:5][CH2:4][OH:3])[C:8](=[O:28])[N:9]([CH3:27])[C:10]=3[N:17]=[CH:16][C:15]=2[O:51][C:47]2[CH:48]=[CH:49][CH:50]=[C:45]([O:44][C:43]([F:42])([F:52])[F:53])[CH:46]=2)=[CH:25][CH:24]=1

참가 물질

9

반응물 4

HCID 673N,N-DimethylglycineHCID 10796Cesium carbonateHCID 27332613-(Trifluoromethoxy)phenolHCID 1188758893-(6-bromo-5-(4-chlorobenzyl)-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate

생성물 1

HCID 1188755345-(4-chlorobenzyl)-3-(3-hydroxypropyl)-1-methyl-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione수율 15.2%

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

To a mixture of 3-(6-bromo-5-(4-chlorobenzyl)-1-methyl-2,4-dioxo-1,2-dihydropyrido[2,3-d]pyrimidin-3(4H)-yl)propyl formate (40 mg, 0.086 mmol), N,N-dimethylglycine (4.4 mg, 0.043 mmol), CuI (2.0 mg, 0.011 mmol), and Cs2CO3 (56 mg, 0.172 mmol) in dioxane (1 mL) was added 3-(trifluoromethoxy)phenol (23 mg, 0.130 mmol). The reaction was heated at 120° C. (MW) for 2 h, cooled to RT then diluted with EA (15 mL) and water (10 mL). The organic layer was washed with water (10 mL) and brine (10 mL), dried over Na2SO4 and concentrated to a residue which was purified by Prep HPLC to give 5-(4-chlorobenzyl)-3-(3-hydroxypropyl)-1-methyl-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (7 mg, 15% yield) as a white solid. 1H NMR (CDCl3) δ: 8.36 (s, 1H), 7.32 (t, J=8.3 Hz, 1H), 7.16 (s, 4H), 6.98 (d, J=8.3 Hz, 1H), 6.75 (dd, J=13.0, 4.7 Hz, 2H), 4.71 (s, 2H), 4.24 (t, J=6.1 Hz, 2H), 3.72 (s, 3H), 3.55 (t, J=5.5 Hz, 2H), 1.98-1.87 (m, 2H). LCMS: MH+ 536 and TR=3.320 min.

후처리

  1. temperatureThe reaction was heated at 120° C. (MW) for 2 h
  2. washThe organic layer was washed with water (10 mL) and brine (10 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated to a residue which
  5. customwas purified by Prep HPLC

출처 및 근거

ORD 기록
ord-0cdeae10d7854a9a97eef2a442af17c3
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09440972B2

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