Citric Acid → HCID 71178972, compound

HRID 2409325Notes

Reaction equation

HRID 2409325 reaction equation
[F:1][C:2]1([F:8])[CH2:4][CH:3]1C(O)=O.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C([N:28]([CH2:31]C)CC)C.[Cl:33][C:34]1[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][C:35]=1[NH:41][C:42]1[N:47]2[N:48]=[CH:49][C:50]([S:51]([NH2:54])(=[O:53])=[O:52])=[C:46]2[N:45]=[CH:44][C:43]=1[C:55]([N:57]1[CH2:62][CH2:61][CH:60]([C:63]2[CH:68]=[CH:67][C:66]([F:69])=[CH:65][CH:64]=2)[CH2:59][CH2:58]1)=[O:56].C(=O)([O-])[O-:71].[K+].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCOCC1>[Cl:33][C:34]1[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][C:35]=1[NH:41][C:42]1[N:47]2[N:48]=[CH:49][C:50]([S:51]([NH:54][C:31](=[O:71])[NH:28][CH:3]3[CH2:4][C:2]3([F:1])[F:8])(=[O:53])=[O:52])=[C:46]2[N:45]=[CH:44][C:43]=1[C:55]([N:57]1[CH2:62][CH2:61][CH:60]([C:63]2[CH:64]=[CH:65][C:66]([F:69])=[CH:67][CH:68]=2)[CH2:59][CH2:58]1)=[O:56]

Participants

8

Reactant 6

HCID 311Citric AcidHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 199401P,P-Diphenylphosphinic azideHCID 27828232,2-Difluorocyclopropane-1-carboxylic acidHCID 71178903HCID 71178903, compound

Product 1

HCID 71178972HCID 71178972, compoundYield 11%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

2,2-Difluorocyclopropanecarboxylic acid (0.067 g, 0.552 mmol) was dissolved in 1,4-dioxane (2 mL), diphenylphosphoryl azide (0.182 g, 0.66 mmol) and triethylamine (0.092 mL, 0.66 mmol) were added, and the mixture was heated under reflux for 2 hr. The reaction solution was allowed to cool, 7-(2-chloro-5-methylphenylamino)-6-[4-(4-fluorophenyl)piperidine-1-carbonyl]pyrazolo[1,5-a]pyrimidine-3-sulfonamide (0.10 g, 0.18 mmol) obtained in Example 12 step 5 and potassium carbonate were added, and the mixture was stirred at 50° C. for 3 hr. 5% Aqueous citric acid solution was added to quench the reaction, and the precipitated crystals were collected by filtration. The obtained crystals were purified by silica gel column chromatography (chloroform/methanol=10/1) to give the title compound (0.014 g, 11%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 2 hr
  3. temperatureto cool
  4. customto quench
  5. customthe reaction
  6. filtrationthe precipitated crystals were collected by filtration
  7. customThe obtained crystals were purified by silica gel column chromatography (chloroform/methanol=10/1)

Sources & evidence

ORD record
ord-48a6fdc326dc435a95b20ef2c9c8a3d1
Source dataset
uspto-grants-2014_08
Patent number
US08815874B2

Reaction notes

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