Sodium Bicarbonate → HCID 58255801, compound

HRID 1695772Notes

Reaction equation

HRID 1695772 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[C:4]([NH:11][C:12]([C:14]2[N:15]=[C:16]([CH3:19])[S:17][CH:18]=2)=[O:13])[CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:44]1[CH:49]=[CH:48][NH:47][C:46](=[O:50])[CH:45]=1.C(=O)(O)[O-].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].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.CC(N(C)C)=O>[CH3:19][C:16]1[S:17][CH:18]=[C:14]([C:12]([NH:11][C:4]2[CH:3]=[C:2]([C:44]3[CH:49]=[CH:48][NH:47][C:46](=[O:50])[CH:45]=3)[CH:10]=[C:9]3[C:5]=2[CH:6]=[N:7][NH:8]3)=[O:13])[N:15]=1

Participants

9

Reactant 5

HCID 516892Sodium Bicarbonate2×HCID 517044Potassium AcetateHCID 8171154-Bromo-2-hydroxypyridineHCID 2733548Bis(pinacolato)diboraneHCID 58255750N-(6-bromo-1H-indazol-4-yl)-2-methyl-1,3-thiazole-4-carboxamide

Product 1

HCID 58255801HCID 58255801, compoundYield 4.8%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 178418397HCID 178418397, compoundCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
80 °C

Procedure

N-(6-Bromo-1H-indazol-4-yl)-2-methyl-1,3-thiazole-4-carboxamide (200 mg, 0.59 mmol), bis(pinacolato)diboron (166 mg, 0.652 mmol), Pd(dppf)Cl2 (48 mg, 0.06 mmol) and potassium acetate (175 mg, 1.78 mmol) were combined in a microwave vial and DMA (10 ml) was added. The solution was degassed and then heated in a Biotage initiator at 80° C. for 20 minutes. More Pd(dppf)Cl2 (48.4 mg, 0.059 mmol) was added, the solution was degassed and heated again at 80° C. for 20 minutes. 4-Bromo-2-pyridone (206 mg, 1.19 mmol), Pd(PPh3)4 (34 mg, 0.03 mmol) and sodium bicarbonate (0.89 ml, 1.78 mmol) were added to the mixture, which was heated under microwave conditions at 150° C. for 15 minutes. Saturated sodium bicarbonate (100 ml) was added to the mixture. The resulting suspension was washed three times with ethyl acetate (100 ml each). A spatula of sodium chloride was added to improve layer separation. Organics were dried and filtered with a hydrophobic frit, combined and dried under vacuum. The solid obtained was preabsorbed on silica and purified on silica (Si) 100 g using a 0-15% methanol-DCM over 60 mins. Appropriate fractions were combined and dried under vacuum. The sample was dissolved in DMSO (1 ml) and purified by MDAP (Method B) eluting with solvents A/B (A: Water+0.1% Formic acid, B: MeCN:Water 95:5+0.05% Formic acid). Pure fractions were combined and dried under vacuum to afford the title compound (10 mg).

Workup

  1. additionwas added
  2. customThe solution was degassed
  3. customthe solution was degassed
  4. temperatureheated again at 80° C. for 20 minutes
  5. temperaturewas heated under microwave conditions at 150° C. for 15 minutes
  6. washThe resulting suspension was washed three times with ethyl acetate (100 ml each)
  7. additionA spatula of sodium chloride was added
  8. customlayer separation
  9. customOrganics were dried
  10. filtrationfiltered with a hydrophobic frit
  11. customdried under vacuum
  12. customThe solid obtained
  13. customwas preabsorbed on silica
  14. custompurified on silica (Si) 100 g
  15. customover 60 mins
  16. customdried under vacuum
  17. dissolutionThe sample was dissolved in DMSO (1 ml)
  18. custompurified by MDAP (Method B)
  19. washeluting with solvents A/B (A: Water+0.1% Formic acid, B
  20. customdried under vacuum

Sources & evidence

ORD record
ord-47e83e8b59de432199f868a0226eaabd
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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