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

反応式

HRID 60448 の反応式
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

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-0cdeae10d7854a9a97eef2a442af17c3
出典データセット
uspto-grants-2016_09
特許番号
US09440972B2

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