Hydrochloric Acid → 4-{[3-Chloro-4-(pyridin-2-ylmethoxy)phenyl]amino}-5,6,7,8-tetrahydrothieno[2,3-b:5,4-c']dipyridine-3-carbonitrile

HRID 38544Notes

Reaction equation

HRID 38544 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:22]([C:23]#[N:24])=[CH:21][N:20]=[C:19]3[S:25][C:26]4[CH2:27][N:28](C(OC(C)(C)C)=O)[CH2:29][CH2:30][C:31]=4[C:18]=23)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.Cl.O1CCOCC1>CC(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:22]([C:23]#[N:24])=[CH:21][N:20]=[C:19]3[S:25][C:26]4[CH2:27][NH:28][CH2:29][CH2:30][C:31]=4[C:18]=23)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 58116804tert-Butyl 4-{[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]amino}-3-cyano-5,8-dihydrothieno[2,3-b:5,4-c']dipyridine-7(6H)-carboxylate

Product 1

HCID 581168904-{[3-Chloro-4-(pyridin-2-ylmethoxy)phenyl]amino}-5,6,7,8-tetrahydrothieno[2,3-b:5,4-c']dipyridine-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

tert-Butyl 4-{[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]amino}-3-cyano-5,8-dihydrothieno[2,3-b:5,4-c′]dipyridine-7(6H)-carboxylate from Example 56A (210 mg, 0.34 mmol) was dissolved in 2-propanol, and 4 M gaseous hydrogen chloride in dioxane (0.17 mL, 0.67 mmol) was added. The mixture was heated to 80° C. for 3 h. The precipitate was collected by suction filtration and dissolved in diluted aqueous sodium hydroxide solution. Some methanol was added, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was evaporated. The title compound was crystallized from dichloromethane/diethyl ether to yield 116 mg (77%).

Workup

  1. filtrationThe precipitate was collected by suction filtration
  2. dissolutiondissolved in diluted aqueous sodium hydroxide solution
  3. additionSome methanol was added
  4. extractionthe mixture was extracted with ethyl acetate
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. customthe solvent was evaporated
  7. customThe title compound was crystallized from dichloromethane/diethyl ether
  8. customto yield 116 mg (77%)

Sources & evidence

ORD record
ord-802aac02377d46a0b45c155427972c5c
Source dataset
uspto-grants-2013_09
Patent number
US08524722B2

Reaction notes

Loading…