Triethylamine → HCID 86657573, compound

HRID 38743Notes

Reaction equation

HRID 38743 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[CH:29]=[CH:28][CH:27]=[C:26]([CH:30]=[O: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[CH2:44][CH2:43][CH:42]([C:39]3[S:40][CH:41]=[C:37]([C:34]4[CH2:33][CH:32]([C:25]5[C:24]([F:23])=[CH:29][CH:28]=[CH:27][C:26]=5[CH:30]=[O:31])[O:36][N:35]=4)[N:38]=3)[CH2:47][CH2:46]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 86657574HCID 86657574, compound

Product 1

HCID 86657573HCID 86657573, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of [3,5-bis-(difluoromethyl)-1H-pyrazol-1-yl]acetic acid (58 mg) in dichloromethane (20 ml) were added, at 0° C., oxalyl chloride (94.5 mg) and one drop of N,N-dimethylformamide. The reaction mixture was stirred at room temperature for 2 hours. The solvent and the excess reagent were removed under reduced pressure. The solid residue was again dissolved in dichloromethane (5 ml) and, at 0° C., added dropwise to a solution of 4-{4-[5-(2-fluoro-6-formylphenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidinium chloride and triethylamine (5.0 eq.) in dichloromethane (15 ml). The reaction mixture was stirred at room temperature overnight. Then it was admixed with concentrated sodium hydrogencarbonate solution, and the aqueous phase was removed and extracted with ethyl acetate. The combined organic phases were dried over sodium sulphate and concentrated. Purification by column chromatography gave 2-{3-[2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazol-4-yl]-4,5-dihydro-1,2-oxazol-5-yl}-3-fluorobenzaldehyde (55 mg).

Workup

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

Sources & evidence

ORD record
ord-e6d0670da6dc407d95181f956bd66a2a
Source dataset
uspto-grants-2013_09
Patent number
US08524743B2

Reaction notes

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