Triethylamine → N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonylmethyl)-3-(2-(pyrrolidin-1-yl)acetamido)benzamide

HRID 1364946Notes

Reaction equation

HRID 1364946 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][C:23]=1[CH2:24][S:25]([CH3:28])(=[O:27])=[O:26])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)[CH:9]=1)=[O:6].[CH2:29]([N:31]([CH2:34][CH3:35])[CH2:32][CH3:33])[CH3:30].BrCC(Br)=[O:39].C(N(C(C)C)C(C)C)C.N1CCCC1>O1CCOCC1>[Cl:14][C:11]1[CH:12]=[CH:13][C:8]([NH:7][C:5](=[O:6])[C:4]2[CH:21]=[CH:22][C:23]([CH2:24][S:25]([CH3:28])(=[O:27])=[O:26])=[C:2]([NH:1][C:30](=[O:39])[CH2:29][N:31]3[CH2:34][CH2:35][CH2:33][CH2:32]3)[CH:3]=2)=[CH:9][C:10]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 31268PyrrolidineHCID 61147Bromoacetyl bromideHCID 81531DiisopropylethylamineHCID 586148873-Amino-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonylmethyl)benzamide

Product 1

HCID 58614720N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonylmethyl)-3-(2-(pyrrolidin-1-yl)acetamido)benzamideYield 21.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

3-Amino-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonylmethyl)benzamide (100 mg, 0.24 mmol) was dissolved in 1,4-dioxane (5.0 ml), treated with triethylamine (274 μL, 1.97 mmol) and 2-bromoacetyl bromide (121 μl, 1.39 mmol). The reaction was heated to reflux for 10 minutes, and stirred at room temperature for 18 hours. The reaction was quenched with water, and extracted twice with ethyl acetate. The ethyl acetate extracts were filtered, washed with water once, brine once, dried with MgSO4, evaporated to 158 mg of a crude brown oil, 3-(2-bromoacetamido)-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonylmethyl)benzamide, which was used without further purification. Crude 3-(2-bromoacetamido)-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl-methyl)benzamide (158 mg) was dissolved in DMF, treated with N-ethyl-N-isopropylpropan-2-amine (61 μl, 0.35 mmol) and pyrrolidine (27 μl, 0.32 mmol), and stirred at room temperature for 18 hours. The reaction was quenched with water and extracted with ethyl acetate twice. The ethyl acetate extracts were washed with water once, brine once, dried with MgSO4, evaporated to a tan solid which was purified by reverse phase HPLC to afford 27 mg of N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonylmethyl)-3-(2-(pyrrolidin-1-yl)acetamido)benzamide as a white powder. MS (Q1) 527 (M)+.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 10 minutes
  3. customThe reaction was quenched with water
  4. extractionextracted twice with ethyl acetate
  5. filtrationThe ethyl acetate extracts were filtered
  6. washwashed with water once
  7. dry with materialbrine once, dried with MgSO4
  8. customevaporated to 158 mg of a crude brown oil, 3-(2-bromoacetamido)-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonylmethyl)benzamide, which
  9. customwas used without further purification
  10. dissolutionCrude 3-(2-bromoacetamido)-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl-methyl)benzamide (158 mg) was dissolved in DMF
  11. stirringstirred at room temperature for 18 hours
  12. customThe reaction was quenched with water
  13. extractionextracted with ethyl acetate twice
  14. washThe ethyl acetate extracts were washed with water once
  15. dry with materialbrine once, dried with MgSO4
  16. customevaporated to a tan solid which
  17. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-f04c0eea77594d52ace318bd17c813d7
Source dataset
uspto-grants-2011_02
Patent number
US07888364B2

Reaction notes

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