Potassium Carbonate → 6-Cyclopropyl-2-(5-(1,1,1-trifluoro-2-(triisopropylsilyloxy)propan-2-yl)-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)pyridin-3-amine

HRID 574211Notes

Reaction equation

HRID 574211 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]2[O:9][C:10]([C:13]([O:19][Si:20]([CH:27]([CH3:29])[CH3:28])([CH:24]([CH3:26])[CH3:25])[CH:21]([CH3:23])[CH3:22])([CH3:18])[C:14]([F:17])([F:16])[F:15])=[N:11][N:12]=2)[C:5]([NH2:30])=[CH:4][C:3]=1[C:31]([F:34])([F:33])[F:32].C([O-])([O-])=O.[K+].[K+].[CH:41]1(B(O)O)[CH2:43][CH2:42]1>O1CCOCC1.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>[CH:41]1([C:2]2[N:7]=[C:6]([C:8]3[O:9][C:10]([C:13]([O:19][Si:20]([CH:21]([CH3:23])[CH3:22])([CH:27]([CH3:28])[CH3:29])[CH:24]([CH3:25])[CH3:26])([CH3:18])[C:14]([F:15])([F:16])[F:17])=[N:11][N:12]=3)[C:5]([NH2:30])=[CH:4][C:3]=2[C:31]([F:32])([F:33])[F:34])[CH2:43][CH2:42]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 867295986-Bromo-2-(5-(1,1,1-trifluoro-2-(triisopropylsilyloxy)propan-2-yl)-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)pyridin-3-amine

Product 1

HCID 867295996-Cyclopropyl-2-(5-(1,1,1-trifluoro-2-(triisopropylsilyloxy)propan-2-yl)-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)pyridin-3-amine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a stirring solution of 6-bromo-2-(5-(1,1,1-trifluoro-2-(triisopropylsilyloxy)propan-2-yl)-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)pyridin-3-amine (step 3) (200 mg, 0.346 mmol) in dry 1,4-dioxane (10 ml) under N2 at RT was added K2CO3 (144 mg, 1.039 mmol) followed by cyclopropylboronic acid (89 mg, 1.039 mmol) and palladiumtetrakis (40.0 mg, 0.035 mmol). The resulting suspension was stirred and heated at reflux (120° C.) overnight for 4 days. The mixture was filtered through Celite® (filter material) and washed through with water (30 ml) and EtOAc (50 ml). The filtrate was separated and the organic portion was dried (MgSO4) and concentrated in vacuo to afford the title compound which was used in the next step without further purification; LC-MS Rt=7.75 min [M+H]+ 539.6 Method 10minLC_v003.

Workup

  1. temperatureheated
  2. filtrationThe mixture was filtered through Celite® (filter material)
  3. washwashed through with water (30 ml) and EtOAc (50 ml)
  4. customThe filtrate was separated
  5. dry with materialthe organic portion was dried (MgSO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ba65951fd97c43e7b5e493c026eb88e8
Source dataset
uspto-grants-2015_05
Patent number
US09034879B2

Reaction notes

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