Acetyl chloride → N-{1-[3-(4-tert-butyl-benzenesulfonylamino)-5-chloro-pyridin-2-yl]-1H-pyrazol-4-yl}acetamide

HRID 75995Notes

Reaction equation

HRID 75995 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][N:5]([C:7]2[C:12]([NH:13][S:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([CH3:26])([CH3:25])[CH3:24])=[CH:19][CH:18]=3)(=[O:16])=[O:15])=[CH:11][C:10]([Cl:27])=[CH:9][N:8]=2)[CH:6]=1.[C:28](Cl)(=[O:30])[CH3:29].C(N(CC)CC)C>>[C:23]([C:20]1[CH:21]=[CH:22][C:17]([S:14]([NH:13][C:12]2[C:7]([N:5]3[CH:6]=[C:2]([NH:1][C:28](=[O:30])[CH3:29])[CH:3]=[N:4]3)=[N:8][CH:9]=[C:10]([Cl:27])[CH:11]=2)(=[O:15])=[O:16])=[CH:18][CH:19]=1)([CH3:24])([CH3:26])[CH3:25]

Participants

4

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 59428137N-[2-(4-amino-pyrazol-1-yl)-5-chloro-pyridin-3-yl]-4-tert-butyl-benzenesulfonamide

Product 1

HCID 59428132N-{1-[3-(4-tert-butyl-benzenesulfonylamino)-5-chloro-pyridin-2-yl]-1H-pyrazol-4-yl}acetamide

Procedure

A solution of N-[2-(4-amino-pyrazol-1-yl)-5-chloro-pyridin-3-yl]-4-tert-butyl-benzenesulfonamide (20 mg, 0.049 mmol), acetyl chloride (3.5 μL, 0.049 mmol), and triethylamine (14 μL, 0.099 mmol) were stirred at room temperature for 1 hour. The reaction was concentrated in vacuo, followed by the addition of dichloromethane (1 mL) and tetrabutylammonium fluoride (0.4 mL, 1.0 M in THF). The reaction was stirred for 2 hours at room temperature and then the crude mixture was partitioned with saturated sodium bicarbonate. The aqueous phase was subsequently extracted with dichloromethane and the combined organic layers dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography (0-100% ethyl acetate in hexanes) to afford N-{1-[3-(4-tert-butyl-benzenesulfonylamino)-5-chloro-pyridin-2-yl]-1H-pyrazol-4-yl}-acetamide: MS (ES) M+H expected 448.1, found 448.0.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. additionfollowed by the addition of dichloromethane (1 mL) and tetrabutylammonium fluoride (0.4 mL, 1.0 M in THF)
  3. customthe crude mixture was partitioned with saturated sodium bicarbonate
  4. extractionThe aqueous phase was subsequently extracted with dichloromethane
  5. dry with materialthe combined organic layers dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash column chromatography (0-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-8ec5bd0110614bb4bf7b8d500d34d9d5
Source dataset
uspto-grants-2014_09
Patent number
US08835468B2

Reaction notes

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