Dimethylformamide → HCID 178433878, compound

HRID 386373Notes

Reaction equation

HRID 386373 reaction equation
S(Cl)([Cl:3])=O.[CH3:5][C:6]1[CH:7]=[C:8]([N:13]2[C:17](=[O:18])[C:16](=[N:19][NH:20][C:21]3[C:22]([OH:36])=[C:23]([C:27]4[CH:32]=[CH:31][CH:30]=[C:29]([C:33](O)=[O:34])[CH:28]=4)[CH:24]=[CH:25][CH:26]=3)[C:15]([CH3:37])=[N:14]2)[CH:9]=[CH:10][C:11]=1[CH3:12].CN(C=O)C>C1COCC1.CCCCCCC>[CH3:5][C:6]1[CH:7]=[C:8]([N:13]2[C:17](=[O:18])/[C:16](=[N:19]\[NH:20][C:21]3[C:22]([OH:36])=[C:23]([C:27]4[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([Cl:3])=[O:34])[CH:28]=4)[CH:24]=[CH:25][CH:26]=3)/[C:15]([CH3:37])=[N:14]2)[CH:9]=[CH:10][C:11]=1[CH3:12]

Participants

6

Reactant 3

HCID 6228Dimethylformamide2×HCID 24386Thionyl Chloride2×HCID 178433881HCID 178433881, compound

Product 1

HCID 178433878HCID 178433878, compoundYield 96%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8900HeptaneSolvent

Procedure

Thionyl chloride (5 mL, 68.5 mmol) was added to a solution of pure 3′-{N′-[1-(3,4-Dimethylphenyl)-3-methyl-5-oxo-1,5-dihydro-pyrazol-4-ylidene]hydrazino}-2′-hydroxybiphenyl-3-carboxylic acid (Eltrombopag form I) (5 g, 11 mmol) in dry THF (75 mL) followed by addition of DMF (0.5 mL) at room temperature in three-necked flask. The reaction mixture was stirred for one hour and additional thionyl chloride (5 mL, 68.5 mmol) and DMF (0.5 mL) were added. The precipitation of acyl chloride started in half an hour and heptane (90 mL) was added. The thick reaction suspension was stirred for further half an hour, filtrated and washed with 2×50 mL of heptane yielding 5 g of (Z)-3′-(2-(1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene)hydrazinyl)-2′-hydroxybiphenyl-3-carbonyl chloride (Yield: 96%); (HPLC: 95%), that was immediately used for the next step.

Workup

  1. customThe precipitation of acyl chloride
  2. waitstarted in half an hour
  3. additionheptane (90 mL) was added
  4. stirringThe thick reaction suspension was stirred for further half an hour
  5. filtrationfiltrated

Sources & evidence

ORD record
ord-f9ef53d68da1470791ce998b312cd7ab
Source dataset
uspto-grants-2013_02
Patent number
US08372822B2

Reaction notes

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