Sodium Carbonate → N-(3-fluoro-4-(1-(4-methoxybenzyl)-3-(3-(methylcarbamoyl)phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 2241262노트

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HRID 2241262 반응식
[CH3:1][O:2][C:3]1[CH:43]=[CH:42][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([N:24]([C:33]5[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=5)[C:25]([C:27]5([C:30]([NH2:32])=[O:31])[CH2:29][CH2:28]5)=[O:26])=[CH:20][C:19]=4[F:40])=[C:11]3[C:10](I)=[N:9]2)=[CH:5][CH:4]=1.[CH3:44][NH:45][C:46]([C:48]1[CH:49]=[C:50](B(O)O)[CH:51]=[CH:52][CH:53]=1)=[O:47].C([O-])([O-])=O.[Na+].[Na+].C(Cl)(Cl)Cl.CO>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:40][C:19]1[CH:20]=[C:21]([N:24]([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)[C:25]([C:27]2([C:30]([NH2:32])=[O:31])[CH2:29][CH2:28]2)=[O:26])[CH:22]=[CH:23][C:18]=1[O:17][C:16]1[CH:15]=[CH:14][N:13]=[C:12]2[N:8]([CH2:7][C:6]3[CH:42]=[CH:43][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[N:9]=[C:10]([C:52]3[CH:51]=[CH:50][CH:49]=[C:48]([C:46](=[O:47])[NH:45][CH3:44])[CH:53]=3)[C:11]=12

참가 물질

7

반응물 4

HCID 10340Sodium CarbonateHCID 27735243-(Methylcarbamoyl)benzeneboronic acidHCID 21584188Chloroform methanolHCID 68512093HCID 68512093, 화합물

생성물 1

HCID 68517924N-(3-fluoro-4-(1-(4-methoxybenzyl)-3-(3-(methylcarbamoyl)phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide수율 35.6%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 80711,2-Dimethoxyethane용매

실험 절차

A stirred mixture of N-(3-fluoro-4-(3-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (100 mg, 0.144 mmol; prepared as in Example 7, Step C), 3-(N-methylaminocarbonyl)phenyl boronic acid (51.47 mg, 0.288 mmol), Pd(PPh3)4 (8.31 mg, 0.0072 mmol) dissolved in 3:1 DME:aqueous 2N Na2CO3 (8 mL) was heated at 70° C. Reaction was monitored by TLC (90/10 CHCl3/MeOH). After stirring for 6 hours, the reaction mixture was partitioned between ethyl acetate (25 mL) and water (50 mL). The organic layer washed with brine, dried over sodium sulfate, filtered and evaporated to afford crude product. The crude was purified by silica gel column chromatography (Biotage 12M) eluting with 2% MeOH/DCM to give the product as pale orange glass (36 mg, 35%). LRMS (APCI pos) m/e 703.2 (M+H).

후처리

  1. customReaction
  2. customthe reaction mixture was partitioned between ethyl acetate (25 mL) and water (50 mL)
  3. washThe organic layer washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customto afford crude product
  8. customThe crude was purified by silica gel column chromatography (Biotage 12M)
  9. washeluting with 2% MeOH/DCM

출처 및 근거

ORD 기록
ord-ab321ebb9bf741ac903446e5d11cf0ad
출처 데이터셋
uspto-grants-2010_05
특허 번호
US07723330B2

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