Cesium carbonate → 1-{6-[3-(Morpholin-4-yl)-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl]pyridin-2-yl}cyclobutanol

HRID 2207354ノート

反応式

HRID 2207354 の反応式
CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:50]1[N:55]=[C:54]([C:56]([F:59])([F:58])[F:57])[CH:53]=[CH:52][N:51]=1.[NH2:60][C:61]1[CH:62]=[C:63]([C:73]2[N:78]=[C:77]([C:79]3([OH:83])[CH2:82][CH2:81][CH2:80]3)[CH:76]=[CH:75][CH:74]=2)[CH:64]=[C:65]([N:67]2[CH2:72][CH2:71][O:70][CH2:69][CH2:68]2)[CH:66]=1>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:67]1([C:65]2[CH:64]=[C:63]([C:73]3[N:78]=[C:77]([C:79]4([OH:83])[CH2:82][CH2:81][CH2:80]4)[CH:76]=[CH:75][CH:74]=3)[CH:62]=[C:61]([NH:60][C:50]3[N:55]=[C:54]([C:56]([F:59])([F:58])[F:57])[CH:53]=[CH:52][N:51]=3)[CH:66]=2)[CH2:72][CH2:71][O:70][CH2:69][CH2:68]1

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27739122-Chloro-4-(trifluoromethyl)pyrimidineHCID 1180927791-[6-[3-Amino-5-(4-morpholinyl)phenyl]-2-pyridinyl]cyclobutanol

生成物 1

HCID 1180925891-{6-[3-(Morpholin-4-yl)-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl]pyridin-2-yl}cyclobutanol

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

Xantphos (93 mg, 0.161 mmol), palladium(II) acetate (24.2 mg, 0.108 mmol), and cesium carbonate (350 mg, 1.08 mmol) were added to a degassed solution of 2-chloro-4-(trifluoromethyl)pyrimidine (103 mg, 0.565 mmol), 1-{6-[3-amino-5-(morpholin-4-yl)phenyl]pyridin-2-yl}cyclobutanol (175 mg, 0.538 mmol) in dioxane (45.3 mL) and the reaction mixture was heated to 100° C. for 2 hours and then for 5 hours at 115° C. Then, the reaction mixture was cooled to room temperature, diluted with water, extracted with ethyl acetate, washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (ethyl acetate:hexanes) to afford 1-{6-[3-(morpholin-4-yl)-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl]pyridin-2-yl}cyclobutanol as an off-white solid. MS APCI calc'd for C24H25F3N5O2 [M+H]+ 472. found 472. 1H NMR (NMR Hz 400 MHz, Acetone-d6): δ 9.26 (s, 1H), 8.82 (d, J=4.8 Hz, 1H), 8.16 (s, 1H), 7.90 (t, J=7.8 Hz, 1H), 7.84-7.77 (m, 2H), 7.66 (d, J=7.8 Hz, 1H), 7.53 (s, 1H), 7.23 (d, J=4.9 Hz, 1H), 3.86 (t, J=4.4 Hz, 4H), 3.30 (t, J=4.4 Hz, 4H), 2.74-2.63 (m, 2H), 2.43 (m, 2H), 2.04 (m, 2H).

後処理

  1. temperatureThen, the reaction mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by silica gel chromatography (ethyl acetate:hexanes)

出典と根拠

ORDレコード
ord-6c2d76a9b29245d99182d5f3776f80bf
出典データセット
uspto-grants-2016_06
特許番号
US09376418B2

反応ノート

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