Cesium carbonate → {6-[7-Bromo-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyrimidin-4-yl}-methanol

HRID 626733ノート

反応式

HRID 626733 の反応式
Br[C:2]1[C:7]2=[CH:8][N:9]([C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[N:10]=[C:6]2[C:5]([Br:19])=[CH:4][N:3]=1.[NH2:20][C:21]1[N:26]=[CH:25][N:24]=[C:23]([CH2:27][OH:28])[CH:22]=1.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+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Br:19][C:5]1[C:6]2[C:7](=[CH:8][N:9]([C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[N:10]=2)[C:2]([NH:20][C:21]2[N:26]=[CH:25][N:24]=[C:23]([CH2:27][OH:28])[CH:22]=2)=[N:3][CH:4]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 21934615(6-Aminopyrimidin-4-yl)methanolHCID 866970594,7-Dibromo-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine

生成物 1

HCID 69671820{6-[7-Bromo-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyrimidin-4-yl}-methanol収率 66%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

実験手順

A suspension of 4,7-dibromo-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine (317 mg, 0.75 mmol), (6-amino-pyrimidin-4-yl)-methanol (104 mg, 0.83 mmol), Pd2(dba)3 (17 mg, 0.019 mmol), Xantphos (43 mg, 0.075 mmol) and cesium carbonate (489 mg, 1.5 mmol) in dioxane (11 mL) was sealed in a microwave vial, purged with nitrogen, and irradiated in a microwave reactor at 150° C. for 1 hour. The reaction mixture was cooled and partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (50-100% ethyl acetate in cyclohexane), to afford the title compound as a white solid (229 mg, 66% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.84 (br s, 1H), 9.31 (s, 1H), 8.72 (d, J=1.2 Hz, 1H), 8.61-8.60 (m, 1H), 8.16 (s, 1H), 7.85 (d, J=1.2 Hz, 1H), 7.83 (s, 1H), 7.74 (dd, J=7.2, 1.6 Hz, 1H), 5.60 (t, J=5.8 Hz, 1H), 4.53 (d, J=5.7 Hz, 2H). LCMS (Method D): RT=3.21 min, m/z: 467 [M+H+].

後処理

  1. customwas sealed in a microwave vial
  2. custompurged with nitrogen
  3. customirradiated in a microwave reactor at 150° C. for 1 hour
  4. temperatureThe reaction mixture was cooled
  5. custompartitioned between ethyl acetate and water
  6. washThe organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel flash chromatography (50-100% ethyl acetate in cyclohexane)

出典と根拠

ORDレコード
ord-251665f9dc3b432ab501a488366abb46
出典データセット
uspto-grants-2016_04
特許番号
US09309240B2

反応ノート

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