Cesium carbonate → 2,6-difluoro-N-[3-(3-{5-fluoro-2-[(3-fluorophenyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]benzamide

HRID 1160018

반응식

HRID 1160018 반응식
Br[C:2]1[CH:3]=[C:4]([C:8]2[C:16]([C:17]3[C:22]([F:23])=[CH:21][N:20]=[C:19]([NH:24][C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[CH:26]=4)[N:18]=3)=[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=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+].[F:80][C:81]1[CH:89]=[CH:88][CH:87]=[C:86]([F:90])[C:82]=1[C:83]([NH2:85])=[O:84]>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]>[F:80][C:81]1[CH:89]=[CH:88][CH:87]=[C:86]([F:90])[C:82]=1[C:83]([NH:85][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[C:16]([C:17]3[C:22]([F:23])=[CH:21][N:20]=[C:19]([NH:24][C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[CH:26]=4)[N:18]=3)=[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][N:10]3[N:9]=2)[CH:3]=1)=[O:84]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 874392,6-DifluorobenzamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59513889HCID 59513889, 화합물

생성물 1

HCID 595137362,6-difluoro-N-[3-(3-{5-fluoro-2-[(3-fluorophenyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]benzamide수율 61%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

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온도
160 °C

실험 절차

A solution 4-[2-(3-bromophenyl)pyrazolo[1,5-a]pyridin-3-yl]-5-fluoro-N-(3-fluorophenyl)-2-pyrimidinamine (40 mg, 84 mmol), Pd2(dba)3 (15.3 mg, 0.016 mmol), xantphos (14.5 mg, 0.025 mmol), Cs2CO3 (95 mg, 0.29 mmol), and 2,6-difluorobenzamide (39 mg, 0.25 mmol) in anhydrous 1,4-dioxane, that had been previously degassed with nitrogen, was heated at 160° C. in the microwave for 15 min. At this time, the crude reaction was adsorbed to silica gel and purified by LC (DCM to 5% MeOH/DCM) to afford the product (28.3 mg, 61%) as a white solid. ESIMS (M+H)+=555. 1H NMR (400 MHz, DMSO-d6) δ 6.63-6.67 (m, 1H), 7.09-7.24 (m, 4H), 7.29-7.49 (m, 3H), 7.54-7.61 (m, 1H), 7.68-7.72 (m, 1H), 7.81 (s, 1H), 7.90-7.94 (m, 1H), 8.04 (m, 1H), 8.09 (m, 1H), 8.53-8.54 (m, 1H), 8.87-8.89 (m, 1H), 9.91 (s, 1H), 10.84 (s, 1H); ESIMS (M+H)+=555.

후처리

  1. customAt this time, the crude reaction
  2. custompurified by LC (DCM to 5% MeOH/DCM)

출처 및 근거

ORD 기록
ord-1732138bc59f4292b3c96b55fe0a0c13
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07812022B2

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