Cesium carbonate → HCID 90204110, compound

HRID 1480108Notes

Reaction equation

HRID 1480108 reaction equation
Br[C:2]1[C:3]([O:10][CH2:11][CH:12]2[CH2:14][CH2:13]2)=[CH:4][C:5]([C:8]#[N:9])=[N:6][CH:7]=1.Cl.[F:16][C:17]1([F:21])[CH2:20][NH:19][CH2:18]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:12]1([CH2:11][O:10][C:3]2[C:2]([N:19]3[CH2:20][C:17]([F:21])([F:16])[CH2:18]3)=[CH:7][N:6]=[C:5]([C:8]#[N:9])[CH:4]=2)[CH2:14][CH2:13]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 27582473,3-Difluoroazetidine hydrochlorideHCID 90203869HCID 90203869, compound

Product 1

HCID 90204110HCID 90204110, compoundYield 99.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 5-Bromo-4-cyclopropylmethoxy-pyridine-2-carbonitrile (Example 53c, 150 mg, 593 μmol) in dry toluene (3.95 ml) under an argon atmosphere in a microwave vial were added 3,3-difluoroazetidine hydrochloride (CAN 288315-03-7, 84.4 mg, 652 μmol), palladium(II) acetate (13.3 mg, 59.3 μmol), BINAP (36.9 mg, 59.3 μmol) and cesium carbonate (386 mg, 1.19 mmol). The reaction mixture was stirred at 120° C. for 45 minutes under microwave radiation. The reaction mixture was filtered over a pad of celite and the filtrate was concentrated in vacuo. The residue was dissolved in ethylacetate and extracted with an aqueous solution of 1.0M sodium bicarbonate. The organic phase was collected, dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a heptane/ethylacetate gradient to yield the title compound (157 mg, 79%) as a white solid. MS (ESI, m/z): 266.2 (M+H+).

Workup

  1. filtrationThe reaction mixture was filtered over a pad of celite
  2. concentrationthe filtrate was concentrated in vacuo
  3. dissolutionThe residue was dissolved in ethylacetate
  4. extractionextracted with an aqueous solution of 1.0M sodium bicarbonate
  5. customThe organic phase was collected
  6. dry with materialdried over sodium sulfate
  7. customevaporated down to dryness
  8. customThe crude material was purified by flash chromatography on silica eluting with a heptane/ethylacetate gradient

Sources & evidence

ORD record
ord-fb1a7982db7045e0a9616c709c671f79
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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