Cesium carbonate → 4-[7-Bromo-4-(6-methyl-pyrimidin-4-ylamino)-pyrazolo[4,3-c]pyridin-2-yl]-3,5-dichlorobenzonitrile

HRID 626728ノート

反応式

HRID 626728 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Cl:21])[C:9]=1[N:10]1[CH:20]=[C:13]2[C:14](Br)=[N:15][CH:16]=[C:17]([Br:18])[C:12]2=[N:11]1)[C:5]#[N:6].[CH3:22][C:23]1[N:28]=[CH:27][N:26]=[C:25]([NH2:29])[CH:24]=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].C(OCC)(=O)C>[Br:18][C:17]1[C:12]2[C:13](=[CH:20][N:10]([C:9]3[C:2]([Cl:1])=[CH:3][C:4]([C:5]#[N:6])=[CH:7][C:8]=3[Cl:21])[N:11]=2)[C:14]([NH:29][C:25]2[CH:24]=[C:23]([CH3:22])[N:28]=[CH:27][N:26]=2)=[N:15][CH:16]=1

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 5728526-Methylpyrimidin-4-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866970583,5-Dichloro-4-(4,7-dibromo-pyrazolo[4,3-c]pyridin-2-yl)-benzonitrile

生成物 1

HCID 696714794-[7-Bromo-4-(6-methyl-pyrimidin-4-ylamino)-pyrazolo[4,3-c]pyridin-2-yl]-3,5-dichlorobenzonitrile収率 57%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

A suspension of 3,5-dichloro-4-(4,7-dibromo-pyrazolo[4,3-c]pyridin-2-yl)-benzonitrile (70 mg, 0.16 mmol), 6-methylpyrimidin-4-ylamine (18 mg, 0.17 mmol), Pd2(dba)3 (7 mg, 0.008 mmol), Xantphos (9 mg, 0.016 mmol) and cesium carbonate (104 mg, 0.31 mmol) in dioxane (3 mL) was sealed in a microwave vial, purged with nitrogen, and heated at 90° C. for 3.5 hours. The reaction mixture was cooled and partitioned between ethyl acetate and water. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resultant residue was purified by silica gel flash chromatography (0-100% ethyl acetate in cyclohexane), then futher triturated with diethyl ether then ethyl acetate to afford the title compound as a white solid (42 mg, 57% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.90 (s, 1H), 9.35 (s, 1H), 8.71 (d, J=1.2 Hz, 1H), 8.50 (s, 2H), 8.37 (s, 1H), 8.17 (s, 1H), 2.45 (s, 3H). LCMS (Method B): RT=3.75 min, m/z: 476 [M+H+].

後処理

  1. customwas sealed in a microwave vial
  2. custompurged with nitrogen
  3. temperatureThe reaction mixture was cooled
  4. custompartitioned between ethyl acetate and water
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resultant residue was purified by silica gel flash chromatography (0-100% ethyl acetate in cyclohexane)
  8. customfuther triturated with diethyl ether

出典と根拠

ORDレコード
ord-2f98c649246c4da9a7f5843b3340379d
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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