Cesium carbonate → N-[6-chloro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl]-2,6-difluorobenzamide

HRID 2089011

反応式

HRID 2089011 の反応式
Cl[C:2]1[CH:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[N:10](S(C3C=CC=CC=3)(=O)=O)[CH:9]=2)[CH:5]=[C:4]([Cl:26])[N:3]=1.[F:27][C:28]1[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[C:29]=1[C:30]([NH2:32])=[O:31].C(=O)([O-])[O-].[Cs+].[Cs+].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>O1CCOCC1.CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:26][C:4]1[N:3]=[C:2]([NH:32][C:30](=[O:31])[C:29]2[C:28]([F:27])=[CH:36][CH:35]=[CH:34][C:33]=2[F:37])[CH:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[NH:10][CH:9]=2)[CH:5]=1

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 874392,6-DifluorobenzamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866498693-(2,6-dichloropyridin-4-yl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine

生成物 1

HCID 49830328N-[6-chloro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl]-2,6-difluorobenzamide収率 8.9%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 6228Dimethylformamide溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
50 °C

実験手順

A mixture of Example 7a (0.100 g, 0.247 mmol), 2,6-difluorobenzamide (0.066 g, 0.421 mmol), cesium carbonate (0.105 g, 0.322 mmol), palladium (II) acetate (2.78 mg, 0.012 mmol), and Xantphos (10.73 mg, 0.019 mmol) in dioxane (3 mL) and DMF (0.1 mL) was heated at 150° C. for 30 minutes in a Biotage microwave reactor. The mixture was concentrated. The solid was suspended in dioxane (3 mL), treated with NaOH (20%, 0.10 mL), and heated at 50° C. for 3 hours. The reaction mixture was concentrated. The residue was stirred in water for 15 minutes, filtered, and purified by reverse-phase HPLC as described in Example 56 to give the title compound (8.5 mg) as trifluoroacetic acid salts. 1H NMR (500 MHz, DMSO-d6) ppm 7.24 (t, J=8.24 Hz, 2H), 7.30 (dd, J=8.09, 4.73 Hz, 1H), 7.52-7.65 (m, 2H), 7.70 (s, 1H), 8.34-8.41 (m, 3H), 8.65 (s, 1H), 11.66 (s, 1H), 12.41 (s, 1H). MS (ESI+) m/z 384.9 (M+H)+.

後処理

  1. concentrationThe mixture was concentrated
  2. additiontreated with NaOH (20%, 0.10 mL)
  3. concentrationThe reaction mixture was concentrated
  4. filtrationfiltered
  5. custompurified by reverse-phase HPLC

出典と根拠

ORDレコード
ord-d4bf6ab631d643248ea99f4a0b804ec7
出典データセット
uspto-grants-2013_05
特許番号
US08435980B2

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