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 2241262Notes

Reaction equation

HRID 2241262 reaction equation
[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

Participants

7

Reactant 4

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

Product 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-dicarboxamideYield 35.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-ab321ebb9bf741ac903446e5d11cf0ad
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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