Ethanol → Sunitinib acid

HRID 1827104Notes

Reaction equation

HRID 1827104 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).

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-7dbbb100b15e42469b1452a94977e7e2
Source dataset
uspto-grants-2006_05
Patent number
US07053114B2

Reaction notes

Loading…