Triethylamine → 3-[5-Amino-4-(3-chlorobenzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methyl-benzamide

HRID 251354Notes

Reaction equation

HRID 251354 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][CH:20]=1)[C:5]([C:7](=[CH:10]NC1C=CC=CC=1)[C:8]#[N:9])=[O:6].FC(F)(F)C(O)=O.[CH:28]1([NH:31][C:32](=[O:42])[C:33]2[CH:38]=[CH:37][C:36]([CH3:39])=[C:35]([NH:40][NH2:41])[CH:34]=2)[CH2:30][CH2:29]1.C(N(CC)CC)C>C(O)C>[NH2:9][C:8]1[N:40]([C:35]2[CH:34]=[C:33]([CH:38]=[CH:37][C:36]=2[CH3:39])[C:32]([NH:31][CH:28]2[CH2:30][CH2:29]2)=[O:42])[N:41]=[CH:10][C:7]=1[C:5](=[O:6])[C:4]1[CH:18]=[CH:19][CH:20]=[C:2]([Cl:1])[CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 67024207N-cyclopropyl-3-hydrazinyl-4-methylbenzamide 2,2,2-trifluoroacetateHCID 670242262-(3-Chlorobenzoyl)-3-phenylaminoacrylonitrile

Product 1

HCID 114408283-[5-Amino-4-(3-chlorobenzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methyl-benzamide

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 2-(3-chlorobenzoyl)-3-phenylaminoacrylonitrile (63 mg, 0.22 mmol, 1.0 eq), N-cyclopropyl-3-hydrazino-4-methylbenzamide trifluoroacetate (72 mg, 0.22 mmol, 1 eq), and triethylamine (31 μL, 0.22 mmol, 1.0 eq) in 10 mL of ethanol was heated to 65° C. for 20h. After cooling, the mixture was concentrated and the residue purified by flash chromatography on silica gel packed and eluted with 7/3 hexanes/ethyl acetate to remove byproducts followed by 3/2 ethyl acetate/hexanes to elute the title compound (33 mg, 38%) as a brown solid. HPLC (4 minute 10-95 gradient) tR 2.35 min; MS m/z 395.1 [M+H]+; 1H NMR (CD3OD), δ 7.92 (d, J=7.2 Hz, 1 H), 7.77 (m, 4 H), 7.55 (m, 3 H), 2.85 (m, 1 H), 2.23 (s, 3 H), 0.80 (d, J=5.5 Hz, 2 H), 0.63 (d, J=2.0 Hz, 2 H) ppm; 13C NMR (CD3OD), δ 187.1, 168.1, 151.9, 141.0, 140.9, 140.0, 134.9, 133.8, 132.8, 130.9, 130.5, 129.4128.1, 127.0, 126.1, 125.6, 102.6, 22.1, 15.7, 4.6 ppm.

Workup

  1. temperatureAfter cooling
  2. concentrationthe mixture was concentrated
  3. customthe residue purified by flash chromatography on silica gel
  4. washeluted with 7/3 hexanes/ethyl acetate
  5. customto remove byproducts
  6. washto elute the title compound (33 mg, 38%) as a brown solid
  7. customHPLC (4 minute 10-95 gradient) tR 2.35 min

Sources & evidence

ORD record
ord-c88552f36c994360941e9ba2c29b7d17
Source dataset
uspto-grants-2011_01
Patent number
US07863314B2

Reaction notes

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