Cesium carbonate → tert-butyl 2-(1H-pyrazol-1-yl)pyridin-4-ylcarbamate

HRID 84866Notes

Reaction equation

HRID 84866 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([N:8]2[CH:12]=[CH:11][CH:10]=[N:9]2)[CH:3]=1.[C:13](=[O:20])([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[NH2:14].C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:8]1([C:4]2[CH:3]=[C:2]([NH:14][C:13](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH:7]=[CH:6][N:5]=2)[CH:12]=[CH:11][CH:10]=[N:9]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 457879024-Bromo-2-(1H-pyrazol-1-yl)pyridine

Product 1

HCID 67514899tert-butyl 2-(1H-pyrazol-1-yl)pyridin-4-ylcarbamate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

Commercial 4-bromo-2-(1H-pyrazol-1-yl)pyridine (500 mg, 2.23 mmol) was dissolved in 30 mL dioxane. To it were added t-butyl carbamate (392 g, 3.35 mmol), cesium carbonate (1.46 g, 4.46 mmol), Pd2(dba)3 (101 mg, 0.11 mmol) and XantPhos (192 mg, 0.33 mmol). The mixture was degassed with Ar stream and stirred under Ar in 85° C. bath for overnight. The mixture was concentrated, taken into 200 mL EtOAc and 100 mL water. The organic phase was separated, dried, concentrated and subjected to flash column (0-20% EtOAc in DCM) to obtain tert-butyl 2-(1H-pyrazol-1-yl)pyridin-4-ylcarbamate. This compound was treated with 2:1 DCM/TFA mixture at RT for 2 h. The mixture was pumped to dryness to afford 2-(1H-pyrazol-1-yl)pyridin-4-amine di-TFA salt.

Workup

  1. customThe mixture was degassed with Ar stream
  2. concentrationThe mixture was concentrated
  3. customThe organic phase was separated
  4. customdried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-b376798f89254934bd4ea2e468debe73
Source dataset
uspto-grants-2014_09
Patent number
US08846928B2

Reaction notes

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