Tetrahydrofuran → HCID 178520269, compound

HRID 45846Notes

Reaction equation

HRID 45846 reaction equation
[F:1][C:2]([F:14])([F:13])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=O)=[CH:5][CH:4]=1.O1CCCC1.ON1C2C=CC=CC=2N=N1.[F:30][C:31]1[C:36]([C:37]2[C:41]([C:42]3[CH:47]=[CH:46][N:45]=[CH:44][CH:43]=3)=[CH:40][NH:39][N:38]=2)=[C:35]([F:48])[CH:34]=[CH:33][C:32]=1[NH2:49]>>[F:30][C:31]1[C:36]([C:37]2[C:41]([C:42]3[CH:47]=[CH:46][N:45]=[CH:44][CH:43]=3)=[CH:40][NH:39][N:38]=2)=[C:35]([F:48])[CH:34]=[CH:33][C:32]=1[NH:49][C:10](=[O:12])[CH2:9][C:6]1[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:14])[F:13])=[CH:8][CH:7]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 757711-HydroxybenzotriazoleHCID 118342(alpha,alpha,alpha-Trifluoro-4-tolyl)acetic acidHCID 178507659HCID 178507659, compound

Product 1

HCID 178520269HCID 178520269, compound

Procedure

To (4-trifluoromethyl-phenyl)-acetic acid (49 mg, 0.24 mmol) in anhydrous tetrahydrofuran (3 mL) 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (63 mg, 0.24 mmol) was added, after 10 minutes 1-hydroxybenzotriazole (38 mg, 0.28 mmol) and after 30 minutes 2,4-difluoro-3-(4-pyridin-4-yl-1H-pyrazol-3-yl)-phenylamine (60 mg, 0.22 mmol) (prepared as described in Example 22) were added. The reaction was stirred under nitrogen atmosphere at room temperature overnight to yield a mixture of mono- and bis-amide (3:1 ratio at 254 nm). The reaction was concentrated under reduced pressure and the residue was dissolved in ethyl acetate, washed successively with NaHCO3 saturated solution and the organic layer was dried over anhydrous sodium sulfate and filtered. The monoamide derivative was isolated by silica gel column chromatography eluting with ethanol 7% in methylene chloride.

Workup

  1. customto yield
  2. concentrationThe reaction was concentrated under reduced pressure
  3. dissolutionthe residue was dissolved in ethyl acetate
  4. washwashed successively with NaHCO3 saturated solution
  5. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customThe monoamide derivative was isolated by silica gel column chromatography
  8. washeluting with ethanol 7% in methylene chloride

Sources & evidence

ORD record
ord-38614a09dc6d4eafb4a8bf46d710531a
Source dataset
uspto-grants-2013_09
Patent number
US08541575B2

Reaction notes

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