Phosphoric Acid → HCID 131734952, compound

HRID 921921Notes

Reaction equation

HRID 921921 reaction equation
[CH3:1][N:2]1[C:6]([CH3:7])=[C:5](B2OC(C)(C)C(C)(C)O2)[C:4]([CH3:17])=[N:3]1.Br[C:19]1[C:20]([Cl:35])=[C:21]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH:22]=[C:23]([C:25]#[N:26])[CH:24]=1.P(=O)(O)(O)O.[K]>C(OCC)(=O)C.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe].O1CCOCC1>[Cl:35][C:20]1[C:19]([C:5]2[C:4]([CH3:17])=[N:3][N:2]([CH3:1])[C:6]=2[CH3:7])=[CH:24][C:23]([C:25]#[N:26])=[CH:22][C:21]=1[NH:27][C:28](=[O:34])[O:29][C:30]([CH3:32])([CH3:31])[CH3:33]

Participants

8

Reactant 4

HCID 1004Phosphoric AcidHCID 27953111,3,5-Trimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 5462222PotassiumHCID 86708481Tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate

Product 1

HCID 131734952HCID 131734952, compoundYield 50.7%

Reagents, catalysts & solvents 3

HCID 178477754HCID 178477754, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A vial was charged with 1,3,5-trimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.117 g, 0.498 mmol), tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate (0.15 g, 0.452 mmol), PdCl2(DPPF) (0.033 g, 0.045 mmol) and dioxane (3.62 ml). The slurry was evacuated and backfilled with nitrogen (4×). Phosphoric acid, potassium salt (0.588 ml, 1.176 mmol) was added and the vial was capped and warmed to 85° C. 2 h. The reaction mixture was diluted with ethyl acetate and vacuum filtered through a pad of Celite. The filtrate was concentrated and the crude residue purified by column chromatography on the ISCO system (12 g, 0-70% EtOAc/Hex) to provide tert-butyl (2-chloro-5-cyano-3-(1,3,5-trimethyl-1H-pyrazol-4-yl)phenyl)carbamate (82.7 mg) as a yellow oil.

Workup

  1. customThe slurry was evacuated
  2. customthe vial was capped
  3. custom2 h
  4. filtrationfiltered through a pad of Celite
  5. concentrationThe filtrate was concentrated
  6. customthe crude residue purified by column chromatography on the ISCO system (12 g, 0-70% EtOAc/Hex)

Sources & evidence

ORD record
ord-aeac87c3753c4277a2a670542ab5987d
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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