Triethylamine → HCID 86719954, compound

HRID 2282994Notes

Reaction equation

HRID 2282994 reaction equation
[F:1][CH:2]([F:15])[C:3]1[CH:7]=[C:6]([CH:8]([F:10])[F:9])[N:5]([CH2:11][C:12]([OH:14])=O)[N:4]=1.C(Cl)(=O)C(Cl)=O.[Cl-].[F:23][C:24]1[C:29]([OH:30])=[CH:28][CH:27]=[C:26]([F:31])[C:25]=1[CH:32]1[O:36][N:35]=[C:34]([C:37]2[N:38]=[C:39]([CH:42]3[CH2:47][CH2:46][NH2+:45][CH2:44][CH2:43]3)[S:40][CH:41]=2)[CH2:33]1.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>ClCCl.CN(C)C=O>[F:15][CH:2]([F:1])[C:3]1[CH:7]=[C:6]([CH:8]([F:9])[F:10])[N:5]([CH2:11][C:12]([N:45]2[CH2:46][CH2:47][CH:42]([C:39]3[S:40][CH:41]=[C:37]([C:34]4[CH2:33][CH:32]([C:25]5[C:26]([F:31])=[CH:27][CH:28]=[C:29]([OH:30])[C:24]=5[F:23])[O:36][N:35]=4)[N:38]=3)[CH2:43][CH2:44]2)=[O:14])[N:4]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 12298443,5-Bis(difluoromethyl)-1H-pyrazole-1-acetic acidHCID 86719955HCID 86719955, compound2×

Product 1

HCID 86719954HCID 86719954, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of [3,5-bis-(difluoromethyl)-1H-pyrazol-1-yl]acetic acid (2 g) in dichloromethane (40 ml) are added, at 0° C., oxalyl chloride (3.273 g) and one drop of N,N-dimethylformamide. The reaction mixture is stirred at room temperature for 2 hours. The solvent and the excess reagent are removed under reduced pressure. The solid residue is again dissolved in dichloromethane (15 ml) and, at 0° C., added dropwise to a solution of 4-{4-[5-(2,6-difluoro-3-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidinium chloride (compound A) and triethylamine (5.0 eq.) in dichloromethane (100 ml). The reaction mixture is stirred at room temperature overnight. Then it is admixed with concentrated sodium hydrogencarbonate solution, and the aqueous phase is removed and extracted with ethyl acetate. The combined organic phases are dried over sodium sulphate and concentrated. Purification by column chromatography gives 2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]-1-(4-{4-[5-(2,6-difluoro-3-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidin-1-yl)ethanone (1.818 g).

Workup

  1. customThe solvent and the excess reagent are removed under reduced pressure
  2. dissolutionThe solid residue is again dissolved in dichloromethane (15 ml) and, at 0° C.
  3. stirringThe reaction mixture is stirred at room temperature overnight
  4. customthe aqueous phase is removed
  5. extractionextracted with ethyl acetate
  6. dry with materialThe combined organic phases are dried over sodium sulphate
  7. concentrationconcentrated
  8. customPurification by column chromatography

Sources & evidence

ORD record
ord-1deca8c6e9b744f5b1cc081290ff72dd
Source dataset
uspto-grants-2015_09
Patent number
US09144238B2

Reaction notes

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