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

HRID 626713ノート

反応式

HRID 626713 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]([Cl: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]>[Cl: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 866970524bromo-7-chloro-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine

生成物 1

HCID 69671775{6-[7-Chloro-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyrimidin-4-yl}-methanol収率 34%

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-bromo-7-chloro-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine (200 mg, 0.53 mmol), (6-amino-pyrimidin-4-yl)-methanol (73 mg, 0.58 mmol), Pd2(dba)3 (24 mg, 0.025 mmol), Xantphos (31 mg, 0.05 mmol) and cesium carbonate (347 mg, 1.1 mmol) in dioxane (3 mL) was sealed in a microwave vial, purged with nitrogen, and irradiated in a microwave reactor at 150° C. for 30 min. 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 NH2 silica gel flash chromatography (0-2% methanol in ethyl acetate), to afford the title compound as a pale yellow solid (57 mg, 34% yield). 1H (400 MHz, DMSO-d6+d-TFA): δ 9.36 (s, 1H), 9.04 (s, 1H), 8.27 (bs, 1H), 8.16 (s, 1H), 7.80 (d, J=1.2 Hz, 1H), 7.78 (s, 1H), 7.70 (dd, J=9.0, 7.3 Hz, 1H), 4.67 (s, 2H). LCMS (Method B): RT=3.19 min, m/z: 421 [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 30 min
  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 NH2 silica gel flash chromatography (0-2% methanol in ethyl acetate)

出典と根拠

ORDレコード
ord-f7803840169e46d38eb99c05ecd23cb5
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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