Triethylamine → HCID 67242423, compound

HRID 38739Notes

Reaction equation

HRID 38739 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-].[Cl:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[C:25]=1[CH:31]1[O:35][N:34]=[C:33]([C:36]2[N:37]=[C:38]([CH:41]3[CH2:46][CH2:45][NH2+:44][CH2:43][CH2:42]3)[S:39][CH:40]=2)[CH2:32]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:44]2[CH2:45][CH2:46][CH:41]([C:38]3[S:39][CH:40]=[C:36]([C:33]4[CH2:32][CH:31]([C:25]5[C:26]([OH:30])=[CH:27][CH:28]=[CH:29][C:24]=5[Cl:23])[O:35][N:34]=4)[N:37]=3)[CH2:42][CH2:43]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 67238250HCID 67238250, compound

Product 1

HCID 67242423HCID 67242423, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of [3,5-bis-(difluoromethyl)-1H-pyrazol-1-yl]acetic acid (177 mg) in dichloromethane (40 ml) are added, at 0° C., oxalyl chloride (290 mg) 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 and, at 0° C., added dropwise to a solution of 4-{4-[5-(2-chloro-6-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidinium chloride and triethylamine (5.0 eq.) in dichloromethane (25 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-chloro-6-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidin-1-yl)ethanone (110 mg).

Workup

  1. customThe solvent and the excess reagent are removed under reduced pressure
  2. dissolutionThe solid residue is again dissolved in dichloromethane 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-efa467241a014c2792c90b7b67af5d2f
Source dataset
uspto-grants-2013_09
Patent number
US08524743B2

Reaction notes

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