Tetrahydrofuran → HCID 178481535, compound

HRID 1921674Notes

Reaction equation

HRID 1921674 reaction equation
C(C1C=CC(C(O)=O)=CC=1)#N.[C:12]([C:14]1[CH:19]=[CH:18][C:17]([C:20]([NH:32][C:33]2[CH:38]=[CH:37][C:36]([C:39]3[N:40]=[CH:41][N:42]([CH3:44])[CH:43]=3)=[CH:35][CH:34]=2)=[C:21]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]([CH3:30])[C:22]2=[O:31])=[CH:16][CH:15]=1)#[N:13].C1COCC1>N.[Ni]>[NH2:13][CH2:12][C:14]1[CH:15]=[CH:16][C:17]([C:20]([NH:32][C:33]2[CH:38]=[CH:37][C:36]([C:39]3[N:40]=[CH:41][N:42]([CH3:44])[CH:43]=3)=[CH:35][CH:34]=2)=[C:21]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]([CH3:30])[C:22]2=[O:31])=[CH:18][CH:19]=1

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 120874-Cyanobenzoic acidHCID 178481534HCID 178481534, compound

Product 1

HCID 178481535HCID 178481535, compound

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 222AmmoniaSolvent

Procedure

Starting from 4-cyanobenzoic acid, synthesis was carried out analogously to Example 40. Only the final step differed as follows. 6.15 g of 3-{(4-cyanophenyl)-[4-(1-methyl-1H-imidazol-4-yl)phenylamino]methylene}-1-methyl-1,3-dihydroindol-2-one was dissolved in 200 mL of methanolic ammonia and THF and hydrogenated with 5 g of Raney nickel at RT and under a pressure of 50 psi. After about 10 hours, the catalyst was removed by suction filtering and the filtrate was again filtered through a glass filter, evaporated down, and the crystalline residue was filtered with diisopropyl ether suction. The crystals were suspended in 400 mL of methanol, adjusted to pH 1 with 10% ethanolic hydrochloric acid, and heated to boiling temperature. The mixture was filtered and the filtrate was evaporated down to a residual volume of about 100 mL and combined with 300 mL of ethanol. After further evaporation to approximately 100 mL residual volume, the substance crystallized out. After cooling, it was suction filtered and washed with ice-cold ethanol. Yield: 6.15 yellow crystals; melting point>300° C.; Rf value=0.32 (dichloromethane/methanol/ammonia (85:15:1)).

Workup

  1. customat RT
  2. customthe catalyst was removed by suction
  3. filtrationfiltering
  4. filtrationthe filtrate was again filtered through a glass
  5. filtrationfilter
  6. customevaporated down
  7. filtrationthe crystalline residue was filtered with diisopropyl ether suction
  8. temperatureheated
  9. filtrationThe mixture was filtered
  10. customthe filtrate was evaporated down to a residual volume of about 100 mL
  11. customAfter further evaporation to approximately 100 mL residual volume
  12. customthe substance crystallized out
  13. temperatureAfter cooling
  14. filtrationfiltered
  15. washwashed with ice-cold ethanol

Sources & evidence

ORD record
ord-8cd945bb3a3f4e0a89bd3ebe0ffa3403
Source dataset
uspto-grants-2012_05
Patent number
US08173699B2

Reaction notes

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