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Toluene → 5-[2-Cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-5,6,7,7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one

HRID 1754806
Notes
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Reaction equation

HRID 1754806 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.[S:12]1[CH:20]2[C:15]([CH2:16][NH:17][CH2:18][CH2:19]2)=[CH:14][C:13]1=[O:21].Br[CH:23]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[F:35])[C:24]([CH:26]1[CH2:28][CH2:27]1)=[O:25].C1COCC1.C1(C)C=CC=CC=1>CN(C=O)C.C(OCC)(=O)C.O.C(#N)C>[CH:26]1([C:24](=[O:25])[CH:23]([N:17]2[CH2:18][CH2:19][CH:20]3[S:12][C:13](=[O:21])[CH:14]=[C:15]3[CH2:16]2)[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[F:35])[CH2:28][CH2:27]1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 4

HCID 1140TolueneHCID 8028TetrahydrofuranHCID 234358712-Bromo-1-cyclopropyl-2-(2-fluorophenyl)ethanoneHCID 451083204-Methylbenzene-1-sulfonic acid--5,6,7,7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one (1/1)

Product 1

HCID 114162775-[2-Cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-5,6,7,7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one

Reagents, catalysts & solvents

4
HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

According to the process of the present invention the 5,6,7,7a-tetrahydro-4H-thieno[3,2-c]pyridine-2-on p-toluenesulfonate (HA=PTSA) of the formula (II) and the 2-bromo-1-cyclopropyl-2-(2-fluorphenyl)-ethanon of the formula (III) are stirred in an organic solvent, (preferably in DMF, THF, toluene, acetonitrile) by adding 1-3 mole equivalent, preferably 2-2.5 mole equivalents of amine, at 20-50° C., preferably 20-30° C., for 1-3, preferably 1-2 hours. The reaction mixture is then divided between water and ethyl acetate and the organic phase is dried and evaporated. The residual product is dissolved in an organic solvent (preferably in DMF, THF, toluene, acetonitrile) without isolating the crystalline 5-[2-cyclopropyl-1-(2-fluorphenyl)-2-oxoethyl]-5,6,7,7a-tetrahydro-4H-thieno[3,2-c]pyridine-2-on of the formula (IV). Then 1-2 equivalent, preferably 1-1.5 equivalent of an amine and 1-3 equivalent, preferably 1-2 equivalent of acetic acid anhydride is added to the reaction mixture and it is further stirred at 20-50° C., preferably 20-30° C., for 1-3 hours, preferably 1-2 hours. The reaction mixture is then divided between water and ethylacetate and the organic phase is dried and evaporated. The remaining product is recrystallized from a suitable organic solvent (acetonitrile, diisopropylether, ethanol), from the mixture of an organic solvent and water or from mixture of suitable organic solvents (toluene-ethyl acetate, hexane-ethyl acetate).

Workup

  1. customat 20-50° C.
  2. custompreferably 20-30° C.
  3. customfor 1-3, preferably 1-2 hours
  4. customthe organic phase is dried
  5. customevaporated
  6. dissolutionThe residual product is dissolved in an organic solvent (preferably in DMF, THF, toluene, acetonitrile)

Sources & evidence

ORD record
ord-f1bbe354259344c69f0c362bca3f7b05
Source dataset
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09169265B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes