Diisopropylethylamine → 2-(3-(bromomethyl)benzamido)-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamide

HRID 926890Notes

Reaction equation

HRID 926890 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[CH:17]=[C:18]([CH:22]=[CH:23][CH:24]=3)[C:19](O)=O)=[O:15])=[C:9]([C:25](=[O:42])[NH:26][C:27]3[CH:31]=[CH:30][N:29]([C:32]4[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[CH:33]=4)[N:28]=3)[CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.[Br:52]CC1C=C(C=CC=1)C(Cl)=O>O1CCCC1>[Br:52][CH2:19][C:18]1[CH:17]=[C:16]([CH:24]=[CH:23][CH:22]=1)[C:14]([NH:13][C:10]1[CH:11]=[CH:12][C:7]([N:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)=[CH:8][C:9]=1[C:25]([NH:26][C:27]1[CH:31]=[CH:30][N:29]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:39])([F:40])[F:41])[CH:33]=2)[N:28]=1)=[O:42])=[O:15]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 144710763-(Bromomethyl)benzoyl chlorideHCID 665880073-((4-(piperidin-1-yl)-2-((1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)carbamoyl)phenyl)carbamoyl)benzoic acid

Product 1

HCID 680701012-(3-(bromomethyl)benzamido)-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamideYield 111%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Into a 50-mL round bottom flask, was placed 2-amino-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamide 8d (100 mg, 0.23 mmol, 1.00 equiv) in tetrahydrofuran (5 mL), and N,N-diisopropylethylamine (60 mg, 0.47 mmol, 2.00 equiv). To this was added 3-(bromomethyl)benzoyl chloride (75 mg, 0.32 mmol, 1.39 equiv), in portions at 0° C. The resulting solution was stirred for 2.5 h at room temperature. The reaction progress was monitored by LCMS/TLC. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 10 mL of water, extracted with 3×10 mL of ethyl acetate, and the organic layers combined. The resulting mixture was washed with 3×10 mL of brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. This resulted in 160 mg (88%) of product as a brown solid.

Workup

  1. customInto a 50-mL round bottom flask, was placed
  2. customat 0° C
  3. concentrationThe resulting mixture was concentrated under vacuum
  4. additionThe resulting solution was diluted with 10 mL of water
  5. extractionextracted with 3×10 mL of ethyl acetate
  6. washThe resulting mixture was washed with 3×10 mL of brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-acf3004f3b1b4fd988d363a2ec4da38f
Source dataset
uspto-grants-2016_03
Patent number
US09289430B2

Reaction notes

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