Sodium Carbonate → HCID 58958602, compound

HRID 915572Notes

Reaction equation

HRID 915572 reaction equation
Br[C:2]1[C:3]([C:16]([CH3:19])([CH3:18])[CH3:17])=[N:4][N:5]([CH3:15])[C:6]=1[NH:7]C(=O)OC(C)(C)C.[N:20]1[CH:25]=[CH:24][CH:23]=[C:22](B(O)O)[CH:21]=1.C([O-])([O-])=O.[Na+].[Na+]>C(O)C.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>[C:16]([C:3]1[C:2]([C:22]2[CH:21]=[N:20][CH:25]=[CH:24][CH:23]=2)=[C:6]([NH2:7])[N:5]([CH3:15])[N:4]=1)([CH3:17])([CH3:18])[CH3:19]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 58958595HCID 58958595, compound2×

Product 1

HCID 58958602HCID 58958602, compoundYield 25.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

tert-Butyl (4-bromo-3-tert-butyl-1-methyl-1H-pyrazol-5-yl)carbamate (Intermediate I, 1.7 g, 5.12 mmol), pyridine-3-boronic acid (1.26 g, 10.23 mmol), and Pd(PPh3)4 (295 mg, 0.26 mmol) were dissolved in ethanol (25 mL), and Na2CO3 (2 M aqueous solution, 25 mL) was added. The mixture was degassed for 10 min. The reaction mixture was then heated to 80° C. for 16 h. The mixture was diluted with ethyl acetate, the solid was filtered off, and the filtrate was treated with TFA (5 mL). The mixture was stirred for 30 min before being concentrated under reduced pressure. The crude was dissolved in methanol and filtered though a C8-silica plug. HPLC purification with gradient elution from 5 to 60% acetonitrile in water afforded 300 mg (25%) of the title compound. 1H NMR (300 MHz, CD3OD) δ 8.73 (d, 1H), 8.64 (s, 1H), 8.14 (d, 1H), 7.81 (dd, 1H), 3.73 (s, 3H), 1.20 (s, 9H). ES-MS m/z 231.2 (MH+); HPLC RT (min) 0.23.

Workup

  1. customThe mixture was degassed for 10 min
  2. additionThe mixture was diluted with ethyl acetate
  3. filtrationthe solid was filtered off
  4. additionthe filtrate was treated with TFA (5 mL)
  5. concentrationbefore being concentrated under reduced pressure
  6. dissolutionThe crude was dissolved in methanol
  7. filtrationfiltered though a C8-silica plug
  8. customHPLC purification
  9. washwith gradient elution from 5 to 60% acetonitrile in water

Sources & evidence

ORD record
ord-559a7cad07be4bc5b97637290e543d4c
Source dataset
uspto-grants-2007_09
Patent number
US07265144B2

Reaction notes

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