Diisopropylethylamine → 5-{[2,4-dichloro-5-(3-fluoropyridin-2-yl)benzoyl]amino}-N-(2-hydroxy-2-methylpropyl)-1-phenyl-1H-pyrazole-3-carboxamide

HRID 522121Notes

Reaction equation

HRID 522121 reaction equation
[Cl:1][C:2]1[CH:24]=[C:23]([Cl:25])[C:22]([C:26]2[C:31]([F:32])=[CH:30][CH:29]=[CH:28][N:27]=2)=[CH:21][C:3]=1[C:4]([NH:6][C:7]1[N:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:10]=[C:9]([C:18](O)=[O:19])[CH:8]=1)=[O:5].C(N(CC)C(C)C)(C)C.[B-](F)(F)(F)F.CN(C(ON1C(=O)C=CC=C1)=[N+](C)C)C.[NH2:62][CH2:63][C:64]([CH3:67])([OH:66])[CH3:65]>CN(C=O)C.C(#N)C>[Cl:1][C:2]1[CH:24]=[C:23]([Cl:25])[C:22]([C:26]2[C:31]([F:32])=[CH:30][CH:29]=[CH:28][N:27]=2)=[CH:21][C:3]=1[C:4]([NH:6][C:7]1[N:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:10]=[C:9]([C:18]([NH:62][CH2:63][C:64]([OH:66])([CH3:67])[CH3:65])=[O:19])[CH:8]=1)=[O:5]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 951022-Propanol, 1-amino-2-methyl-HCID 2733204O-(2-Oxo-1(2H)-pyridyl)-N,N,N',N'-tetramethyluronium TetrafluoroborateHCID 1184970555-(2,4-dichloro-5-(3-fluoropyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylic acid

Product 1

HCID 1184970845-{[2,4-dichloro-5-(3-fluoropyridin-2-yl)benzoyl]amino}-N-(2-hydroxy-2-methylpropyl)-1-phenyl-1H-pyrazole-3-carboxamideYield 66.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
10 °C

Procedure

5-(2,4-dichloro-5-(3-fluoropyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylic acid (Example 107, 78 g, 166 mmol) was sonicated in DMF (300 mL) with N,N-diisopropylethylamine (58 mL, 332 mmol) to give a clear solution, which was cooled to 10° C. TPTU (74 g, 249 mmol) was added portionwise and the mixture stirred at 10° C. for 20 minutes. A solution of 1-amino-2-methylpropan-2-ol (22.1 g, 249 mmol) in DMF (50 mL) was added dropwise at 10° C. and the mixture then allowed to warm to room temperature and stirred for 16 hours. The reaction mixture was partitioned between EtOAc (600 mL) and water (600 mL). The aqueous layer was separated and extracted with additional EtOAc (3×200 mL). The combined organic layers were washed with saturated aqueous ammonium chloride solution (300 mL), water (5×200 mL), dried (magnesium sulphate) and concentrated in vacuo to give an orange oil. The oil was treated with acetonitrile (300 mL) and the resulting solid collected by filtration, washed with acetonitrile and dried under vacuum to afford the title compound as a colourless solid (60 g, 66%).

Workup

  1. customto give a clear solution, which
  2. temperatureto warm to room temperature
  3. stirringstirred for 16 hours
  4. customThe reaction mixture was partitioned between EtOAc (600 mL) and water (600 mL)
  5. customThe aqueous layer was separated
  6. extractionextracted with additional EtOAc (3×200 mL)
  7. washThe combined organic layers were washed with saturated aqueous ammonium chloride solution (300 mL), water (5×200 mL)
  8. dry with materialdried (magnesium sulphate)
  9. concentrationconcentrated in vacuo
  10. customto give an orange oil
  11. filtrationthe resulting solid collected by filtration
  12. washwashed with acetonitrile
  13. customdried under vacuum

Sources & evidence

ORD record
ord-56bae0fc9f4048b4b5a9e997c48cf362
Source dataset
uspto-grants-2016_05
Patent number
US09328096B2

Reaction notes

Loading…