Sodium Carbonate → HCID 86633644, compound

HRID 1798496Notes

Reaction equation

HRID 1798496 reaction equation
C(OC([N:8]1[CH:12]=[C:11](B2OC(C)(C)C(C)(C)O2)[CH:10]=[N:9]1)=O)(C)(C)C.C([O-])([O-])=O.[Na+].[Na+].Br[C:29]1[CH:30]=[C:31]([C:35]2[CH:40]=[C:39]([NH:41][CH2:42][CH2:43][C:44]3[C:52]4[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=4)[NH:46][CH:45]=3)[N:38]=[C:37]([C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][N:54]=3)[CH:36]=2)[CH:32]=[N:33][CH:34]=1>CN1C(=O)CCC1.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH:46]1[C:47]2[C:52](=[CH:51][CH:50]=[CH:49][CH:48]=2)[C:44]([CH2:43][CH2:42][NH:41][C:39]2[N:38]=[C:37]([C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][N:54]=3)[CH:36]=[C:35]([C:31]3[CH:32]=[N:33][CH:34]=[C:29]([C:11]4[CH:12]=[N:8][NH:9][CH:10]=4)[CH:30]=3)[CH:40]=2)=[CH:45]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 44137783HCID 44137783, compound

Product 1

HCID 86633644HCID 86633644, compound

Reagents, catalysts & solvents 2

HCID 10974057(Butane-1,4-diyl)bis(diphenylphosphane)--dichloropalladium (1/1)CatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazole-1-carboxylic acid tert-butyl ester (1.1 eq, 0.12 mmol, 34 mg) is stirred in NMP (1 ml) and 2M Na2CO3 (2 eq, 0.21 mmol, 0.106 ml) for 15 minutes, under an inert atmosphere of argon. (5″-Bromo-[2,2′;4′,3″]terpyridin-6′-yl)-[2-(1H-indol-3-yl)-ethyl]-amine (Example 1.14) (1 eq, 0.11 mmol, 50 mg) and 1,4-bis(diphenylphosphino)butane-palladium(II) chloride (0.2 eq, 0.021 mmol, 12 mg) are added and the reaction mixture is flushed with argon and heated using microwave radiation at 100° C. for 2 hours. The reaction mixture is extracted into EtOAc washing with water. The organic phase is washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The crude residue is purified by reverse phase column chromatography (Isolute™ C18, 0-50% acetonitrile in water—0.1% TFA) and the appropriate fractions are combined and concentrated in vacuo. The resulting residue is dissolved in MeOH and loaded onto a SCX-2 cartridge eluting with MeOH followed by 2M NH3 in MeOH. The methanolic ammonia fractions are concentrated in vacuo and dried under vacuum to afford the title compound; [M+H]+ 458.

Workup

  1. customthe reaction mixture is flushed with argon
  2. temperatureheated
  3. customat 100° C.
  4. customfor 2 hours
  5. extractionThe reaction mixture is extracted into EtOAc washing with water
  6. washThe organic phase is washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude residue is purified by reverse phase column chromatography (Isolute™ C18, 0-50% acetonitrile in water—0.1% TFA)
  11. concentrationconcentrated in vacuo
  12. dissolutionThe resulting residue is dissolved in MeOH
  13. washeluting with MeOH
  14. concentrationThe methanolic ammonia fractions are concentrated in vacuo
  15. customdried under vacuum

Sources & evidence

ORD record
ord-3283667f77144b25a69d0f67836c7a15
Source dataset
uspto-grants-2013_01
Patent number
US08343966B2

Reaction notes

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