Diisopropylethylamine → HCID 11386291, compound

HRID 1643256Notes

Reaction equation

HRID 1643256 reaction equation
[I:1][C:2]1[C:6]([C:7](O)=[O:8])=[CH:5][N:4]([CH3:10])[N:3]=1.[Cl:11][C:12]1[CH:13]=[C:14]([C:19]2[C:20]([NH2:26])=[CH:21][CH:22]=[C:23]([F:25])[CH:24]=2)[CH:15]=[CH:16][C:17]=1[Cl:18].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1>C(Cl)Cl>[Cl:11][C:12]1[CH:13]=[C:14]([C:19]2[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=2[NH:26][C:7]([C:6]2[C:2]([I:1])=[N:3][N:4]([CH3:10])[CH:5]=2)=[O:8])[CH:15]=[CH:16][C:17]=1[Cl:18]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 114140693-Iodo-1-methyl-1H-pyrazole-4-carboxylic acidHCID 115724193',4'-Dichloro-5-fluoro-[1,1'-biphenyl]-2-amine

Product 1

HCID 11386291HCID 11386291, compoundYield 56.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

At room temperature, 273 mg (1.0 mmol) of 3-iodo-1-methyl-1H-pyrazole-4-carboxylic acid, 213 mg (0.83 mmol) of 3′,4′-dichloro-5-fluorobiphenyl-2-amine, 0.3 ml (1.67 mmol) of N,N-diisopropyl-ethylamine and 583 mg (1.25 mmol) of bromotripyrrolidinophosphonium hexafluorophosphate were stirred in 5 ml of methylene chloride for 3 days. The mixture was washed with saturated sodium bicarbonate solution and then with water. Removal and concentration of the organic phase gave 910 mg of crude product. Purification by column chromatography on silica gel 60 using methylene chloride/diethyl ether 5:1 gave 230 mg (53.5% of theory) of N-(3′,4′-dichloro-5-fluoro-1,1′-biphenyl-2-yl)-3-iodo-1-methyl-1H-pyrazole-4-carboxamide (compound No. 6 from table 1) of logP (pH 2.3)=3.42.

Workup

  1. washThe mixture was washed with saturated sodium bicarbonate solution
  2. customRemoval and concentration of the organic phase
  3. customgave 910 mg of crude product
  4. customPurification by column chromatography on silica gel 60 using methylene chloride/diethyl ether 5:1

Sources & evidence

ORD record
ord-ad881c0d787345f48ced1f08f57de99b
Source dataset
uspto-grants-2012_02
Patent number
US08119682B2

Reaction notes

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