Ethanol → Sunitinib acid

HRID 2252213Notes

Reaction equation

HRID 2252213 reaction equation
[CH:1]([C:3]1[NH:7][C:6]([CH3:8])=[C:5]([C:9]([OH:11])=[O:10])[C:4]=1[CH3:12])=O.[F:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[NH:19][C:18](=[O:23])[CH2:17]2.C(O)C.N1CCCC1>C(O)(=O)C>[F:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[NH:19][C:18](=[O:23])/[C:17]/2=[CH:1]\[C:3]1[NH:7][C:6]([CH3:8])=[C:5]([C:9]([OH:11])=[O:10])[C:4]=1[CH3:12]

Participants

6

Reactant 4

HCID 702EthanolHCID 31268PyrrolidineHCID 37310125-fluoro-1,3-dihydro-2H-indol-2-oneHCID 110737925-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic Acid

Product 1

HCID 10979489Sunitinib acidYield 79%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

5-Formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (61 g), 5-fluoro-1,3-dihydro-indol-2-one (79 g), ethanol (300 mL) and pyrrolidine (32 mL) were refluxed for 4.5 hours. Acetic acid (24 mL) was added to the mixture and refluxing was continued for 30 minutes. The mixture was cooled to room temperature and the solids collected by vacuum filtration and washed twice with ethanol. The solids were stirred for 130 minutes in 40% acetone in water (400 mL) containing 12 N hydrochloric acid (6.5 mL). The solids were collected by vacuum filtration and washed twice with 40% acetone in water. The solids were dried under vacuum to give 5-[5-fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (86 g, 79% yield) as an orange solid. 1H-NMR (dimethylsulfoxide-d6) δ 2.48, 2.50 (2×s, 6H, 2×CH3), 6.80, 6.88, 7.68, 7.72 (4×m, 4H, aromatic and vinyl), 10.88 (s, 1H, CONH), 12.12 (s, 1H, COOH), 13.82 (s, 1H, pyrrole NH). MS m/z 299 [M−1].

Workup

  1. temperaturerefluxing
  2. filtrationthe solids collected by vacuum filtration
  3. washwashed twice with ethanol
  4. additioncontaining 12 N hydrochloric acid (6.5 mL)
  5. filtrationThe solids were collected by vacuum filtration
  6. washwashed twice with 40% acetone in water
  7. customThe solids were dried under vacuum

Sources & evidence

ORD record
ord-acf99c3060f2468384b375ed144f219e
Source dataset
uspto-grants-2008_01
Patent number
US07320996B2

Reaction notes

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