Sodium Carbonate → HCID 117700166, compound

HRID 1049146Notes

Reaction equation

HRID 1049146 reaction equation
[C:1]([CH2:3][C:4]1([N:15]2[CH:19]=[C:18](B3OC(C)(C)C(C)(C)O3)[CH:17]=[N:16]2)[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:5]1)#[N:2].Br[C:30]1[C:31]([CH3:36])=[N:32][NH:33][C:34]=1[CH3:35].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.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:1]([CH2:3][C:4]1([N:15]2[CH:19]=[C:18]([C:30]3[C:31]([CH3:36])=[N:32][NH:33][C:34]=3[CH3:35])[CH:17]=[N:16]2)[CH2:5][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:7]1)#[N:2]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 769374-bromo-3,5-dimethyl-1H-pyrazoleHCID 67457197tert-butyl 3-(cyanomethyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)azetidine-1-carboxylate

Product 1

HCID 117700166HCID 117700166, compoundYield 26%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of tert-butyl 3-(cyanomethyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidine-1-carboxylate (381 mg, 0.981 mmol, from Example 1, step 2), 4-bromo-3,5-dimethyl-1H-pyrazole (206 mg, 1.18 mmol), tetrakis(triphenylphosphine)palladium(0) (110 mg, 0.098 mmol) and sodium carbonate (310 mg, 2.9 mmol) in 1,4-dioxane (10 mL) and water (5 mL) was purged with N2 and stirred at 110° C. for 2 h. The reaction mixture was filtered, diluted with EtOAc, then washed with water. The organic layer was concentrated and purified on silica gel (eluting with 0-100% EtOAc/hexanes followed by 0-10% MeOH/dichloromethane) to give tert-butyl 3-(cyanomethyl)-3-(3′,5′-dimethyl-1H,1′H-4,4′-bipyrazol-1-yl)azetidine-1-carboxylate (90 mg, 26%). LCMS calculated for C18H25N6O2 (M+H)+: m/z=357.2. Found: 357.2. This intermediate was treated with 4.0 M hydrogen chloride in dioxane (1.2 mL, 4.9 mmol) in methylene chloride (1 mL) at rt for 2 h. The mixture was stripped to dryness to give the desired product. LCMS calculated for C13H17N6 (M+H)+: m/z=257.1. Found: 257.1.

Workup

  1. customwas purged with N2
  2. filtrationThe reaction mixture was filtered
  3. additiondiluted with EtOAc
  4. washwashed with water
  5. concentrationThe organic layer was concentrated
  6. custompurified on silica gel (eluting with 0-100% EtOAc/hexanes followed by 0-10% MeOH/dichloromethane)

Sources & evidence

ORD record
ord-9665aa18b5f147468081af058a0b7eda
Source dataset
uspto-grants-2016_07
Patent number
US09382231B2

Reaction notes

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