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

HRID 2089011

반응식

HRID 2089011 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 6228Dimethylformamide용매HCID 312751,4-Dioxane용매

반응 조건

온도
50 °C

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-d4bf6ab631d643248ea99f4a0b804ec7
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08435980B2

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