Cesium carbonate → HCID 90203799, compound

HRID 1480158Notes

Reaction equation

HRID 1480158 reaction equation
[OH:1][NH:2][C:3]([C:5]([NH:12][C:13]([C:15]1[CH:20]=[C:19]([O:21][CH2:22][C:23]([F:26])([F:25])[F:24])[C:18](Br)=[CH:17][N:16]=1)=[O:14])([CH3:11])[CH2:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[NH:4].[CH:28]1([B-](F)(F)F)[CH2:30][CH2:29]1.[K+].[CH2:36](P(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2)[CH2:37]CC.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:11][C:5]([NH:12][C:13]([C:15]1[CH:20]=[C:19]([O:21][CH2:22][C:23]([F:26])([F:25])[F:24])[C:18]([CH:28]2[CH2:30][CH2:29]2)=[CH:17][N:16]=1)=[O:14])([C:3]1[N:4]=[C:36]([CH3:37])[O:1][N:2]=1)[CH2:6][C:7]([CH3:10])([CH3:9])[CH3:8]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 23697338Potassium cyclopropyltrifluoroborateHCID 178443997HCID 178443997, compound

Product 1

HCID 90203799HCID 90203799, compoundYield 957.9%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
125 °C

Procedure

To a solution of 5-Bromo-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid [1-(N-hydroxycarbamimidoyl)-1,3,3-trimethyl-butyl]-amide (Example 97c, 0.175 g, 365 μmol) in toluene (2 ml) under an argon atmosphere was added potassium cyclopropytrifluoroborate (108 mg, 730 μmol), palladium (II) acetate (4.1 mg, 18.3 μmol), butyldi-1-adamantylphosphine (13.1 mg, 36.5 μmol) and cesium carbonate (243 μl, 730 μmol). The reaction was stirred at 125° C. for 18 hours. The reaction was filtered through a pad of celite. The filtrate was diluted with ethylacetate and was extracted with an 1.0M aqueous solution of sodium bicarbonate. The organic phase was 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 (154 mg, 96%) as a light yellow oil. MS (ESI, m/z): 441.7 (M+H+).

Workup

  1. filtrationThe reaction was filtered through a pad of celite
  2. additionThe filtrate was diluted with ethylacetate
  3. extractionwas extracted with an 1.0M aqueous solution of sodium bicarbonate
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. customevaporated down to dryness
  6. customThe crude material was purified by flash chromatography on silica eluting with a heptane/ethylacetate gradient

Sources & evidence

ORD record
ord-7ed7c0eed6a547c78de65177b15565f0
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

Loading…