Cesium carbonate → 1-{6-[2-(2,6-Dichlorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyrimidin-4-yl}-ethanol

HRID 626751

反応式

HRID 626751 の反応式
Cl[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[CH:5]=[CH:4][N:3]=1.[NH2:19][C:20]1[N:25]=[CH:24][N:23]=[C:22]([CH:26]([OH:28])[CH3:27])[CH:21]=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]>[Cl:18][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]([Cl:17])[C:11]=1[N:9]1[CH:8]=[C:7]2[C:2]([NH:19][C:20]3[N:25]=[CH:24][N:23]=[C:22]([CH:26]([OH:28])[CH3:27])[CH:21]=3)=[N:3][CH:4]=[CH:5][C:6]2=[N:10]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 696711341-(6-Aminopyrimidin-4-yl)-ethanolHCID 866970364-chloro-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine

生成物 1

HCID 696718161-{6-[2-(2,6-Dichlorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyrimidin-4-yl}-ethanol収率 21%

試薬・触媒・溶媒 2

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

反応条件

温度
150 °C

実験手順

A mixture of 4-chloro-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine (133 mg, 0.445 mmol), 1-(6-aminopyrimidin-4-yl)-ethanol (65 mg, 0.467 mmol), Pd2(dba)3 (20 mg, 0.022 mmol), Xantphos (26 mg, 0.045 mmol) and cesium carbonate (290 mg, 0.89 mmol) in dioxane (3.5 mL) was de-gassed and purged with nitrogen and the reaction mixture was heated at 150° C. in the microwave for 30 minutes. The resultant mixture was filtered and washed with dioxane. The filtrate was concentrated under reduced pressure and the resultant residue was purified by silica gel flash chromatography (0-100% ethyl acetate in cyclohexane) to afford a yellow solid. This was re-purified by HPLC [gradient: 5 to 98% acetonitrile (0.1% ammonium hydroxide) in water (0.1% ammonium hydroxide)], to afford the title compound as a white solid (31 mg, 21% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.53 (d, J=0.9 Hz, 1H), 9.07 (d, J=1.1 Hz, 1H), 8.09 (d, J=7.3 Hz, 1H), 7.88-7.86 (m, 2H), 7.78 (dd, J=9.2, 7.1 Hz, 1H), 7.68-7.61 (m, 2H), 4.83-4.76 (m, 1H), 1.46 (d, J=6.7 Hz, 3H). LCMS (Method B): RT=2.74 min, m/z: 401 [M+H+].

後処理

  1. customwas de-gassed
  2. custompurged with nitrogen
  3. filtrationThe resultant mixture was filtered
  4. washwashed with dioxane
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe resultant residue was purified by silica gel flash chromatography (0-100% ethyl acetate in cyclohexane)
  7. customto afford a yellow solid
  8. customThis was re-purified by HPLC [gradient: 5 to 98% acetonitrile (0.1% ammonium hydroxide) in water (0.1% ammonium hydroxide)]

出典と根拠

ORDレコード
ord-035dbd663cb34395878ff0a08ddfd968
出典データセット
uspto-grants-2016_04
特許番号
US09309240B2

関連ノート

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