Triethylamine → 2-(3-Chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid [2-(bicyclopropyl-1-ylcarbamoyl)-4-iodo-6-methyl-phenyl]-amide

HRID 1819276Notes

Reaction equation

HRID 1819276 reaction equation
[Cl:1][C:2]1[C:3]([N:8]2[C:12]([C:13]3[O:14][C:15](=[O:25])[C:16]4[CH:22]=[C:21]([I:23])[CH:20]=[C:19](O)[C:17]=4[N:18]=3)=[CH:11][C:10]([C:26]([F:29])([F:28])[F:27])=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.Cl.[C:31]1([NH2:37])([CH:34]2[CH2:36][CH2:35]2)[CH2:33][CH2:32]1.[CH2:38](N(CC)CC)C>C1COCC1>[C:31]1([NH:37][C:15]([C:16]2[CH:22]=[C:21]([I:23])[CH:20]=[C:19]([CH3:38])[C:17]=2[NH:18][C:13]([C:12]2[N:8]([C:3]3[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][N:4]=3)[N:9]=[C:10]([C:26]([F:28])([F:29])[F:27])[CH:11]=2)=[O:14])=[O:25])([CH:34]2[CH2:36][CH2:35]2)[CH2:33][CH2:32]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 53433499(1,1'-Bi(cyclopropan))-1-amine hydrochlorideHCID 1363549442-[2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-8-hydroxy-6-iodo-benzo[d][1,3]oxazin-4-one

Product 1

HCID 578872022-(3-Chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid [2-(bicyclopropyl-1-ylcarbamoyl)-4-iodo-6-methyl-phenyl]-amide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2.08 g (3.91 mmol) (2-[2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-8-hydroxy-6-iodo-benzo[d][1,3]oxazin-4-one (prepared according to WO 04/067528), 0.6 g (4.50 mmol) bicyclopropyl-1-ylamine hydrochloride and 0.63 ml (4.50 mmol) triethylamine in 20 ml THF are heated 20 h at reflux. After cooling down, the precipitate is filtered and the mother liquor is evaporated. The residue is dissolved in 5 ml DMF and poured into 40 ml water. The crystals formed are filtered and purified by flash-chromatography (dichloromethane 40, diethylether 1) to afford 1.85 g title compound. 1H-NMR (CDCl3, 400 MHz. ppm): 0.11 (q, 2H), 0.45 (q, 2H), 0.62 (s, 4H), 1.4 (m, 1H), 2.10 (s, 3H), 6.50 (s, 1H), 7.40 (m, 2H), 7.51 (s, 1H), 7.77 (s, 1H), 7.85 (dd, 1H), 8.49 (m, 1H), 10.45 (s, 1H).

Workup

  1. temperatureat reflux
  2. temperatureAfter cooling down
  3. filtrationthe precipitate is filtered
  4. customthe mother liquor is evaporated
  5. dissolutionThe residue is dissolved in 5 ml DMF
  6. additionpoured into 40 ml water
  7. customThe crystals formed
  8. filtrationare filtered
  9. custompurified by flash-chromatography (dichloromethane 40, diethylether 1)

Sources & evidence

ORD record
ord-5010a50d7448408a8422d1512ca7ce70
Source dataset
uspto-grants-2009_10
Patent number
US07601743B2

Reaction notes

Loading…