Tosylmethyl isocyanide → HCID 69075280, compound

HRID 225484Notes

Reaction equation

HRID 225484 reaction equation
CC(C)([O-])C.[K+].[Cl:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([C:15]2[N:16]=[C:17]([N:24]3[CH2:30][CH2:29][CH2:28][C:27](=O)[CH2:26][CH2:25]3)[C:18]3[S:23][CH:22]=[CH:21][C:19]=3[N:20]=2)=[C:10]([F:32])[CH:9]=1.C1(C)C=CC(S([CH2:42][N+:43]#[C-])(=O)=O)=CC=1.Cl.CCOC(C)=O>CCOC(C)=O.C1COCC1.COCCOC>[ClH:7].[Cl:7][C:8]1[C:13]([F:14])=[CH:12][C:11]([C:15]2[N:16]=[C:17]([N:24]3[CH2:30][CH2:29][CH2:28][CH:27]([C:42]#[N:43])[CH2:26][CH2:25]3)[C:18]3[S:23][CH:22]=[CH:21][C:19]=3[N:20]=2)=[C:10]([F:32])[CH:9]=1

Participants

8

Reactant 4

HCID 161915Tosylmethyl isocyanideHCID 21866389Hydrogen chloride-ethyl acetateHCID 23665647Potassium tert-butoxideHCID 69076453HCID 69076453, compound

Product 1

HCID 69075280HCID 69075280, compoundYield 41.2%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

440 mg of potassium tert-butoxide was added to a mixture of 650 mg of 1-[2-(4-chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine-4-yl]azepane-4-one, 380 mg of p-toluensulfonylmethyl isocyanide, 20 ml of 1,2-dimethoxyethane and 10 ml of THF and the resultant was stirred for one hour under ice cooling. After the reaction mixture was concentrated under reduced pressure, 50 ml of water was added to the obtained residue and extracted twice with 100 ml of EtOAc. After the organic layer washed with a saturated saline solution and dried over anhydrous magnesium sulfate, the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography chloroform-MeOH) and a foam-like substance was obtained. 50 ml of EtOAc and 0.5 ml of 4M HCl-EtOAc solution were added to the foam-like substance and the solvent was removed under reduced pressure to give a solid. The obtained solid was washed with ethyl acetate to give 150 mg of 1-[2-(4-chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine-4-yl]azepane-4-carbonitrile hydrochloride.

Workup

  1. concentrationAfter the reaction mixture was concentrated under reduced pressure, 50 ml of water
  2. additionwas added to the obtained residue
  3. extractionextracted twice with 100 ml of EtOAc
  4. washAfter the organic layer washed with a saturated saline solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was removed under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography chloroform-MeOH) and a foam-like substance
  8. customwas obtained
  9. customthe solvent was removed under reduced pressure
  10. customto give a solid
  11. washThe obtained solid was washed with ethyl acetate

Sources & evidence

ORD record
ord-9d4fd6d2f0ed4da6807f6b789fe79a9a
Source dataset
uspto-grants-2009_07
Patent number
US07557112B2

Reaction notes

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