Dimethylformamide → HCID 68183104, compound

HRID 1615575Notes

Reaction equation

HRID 1615575 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][NH:12][C:11](=[O:14])[C:10]3[S:15][C:16]([N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)=[CH:17][C:9]2=3)=[CH:4][CH:3]=1.CN(C=O)C.[Br:29]N1C(=O)CCC1=O>>[Br:29][C:17]1[C:9]2[CH:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)[CH2:13][NH:12][C:11](=[O:14])[C:10]=2[S:15][C:16]=1[N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 67184N-bromobutanimideHCID 68183085HCID 68183085, compound

Product 1

HCID 68183104HCID 68183104, compound

Procedure

To a solution of 4-(4-chlorophenyl)-2-(morpholin-4-yl)-5,6-dihydrothieno[2,3-c]pyridin-7(4H)-one (0.478 g, 1.37 mmol, single enantiomer of unknown absolute configuration) in DMF (8.9 mL, 110 mmol) was added N-bromosuccinimide (0.2561 g, 1.439 mmol), and the mixture was stirred at room temperature for 2 hours. Reaction was quenched via addition of 10% aqueous sodium thiosulfate solution (30 mL), and then diluted with EtOAc (100 mL) and water (10 mL) with sonication to encourage complete dissolution of solids. The layers were separated, and aqueous layer was extracted 1×EtOAc (50 mL). The combined organic layers were washed 1× brine (10 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was adsorbed to Celite (15 mL) and dryloaded onto a silica gel column. Column chromatography (eluent: 0-100% EtOAc:hexanes) then afforded 3-bromo-4-(4-chlorophenyl)-2-(morpholin-4-yl)-5,6-dihydrothieno[2,3-c]pyridin-7(4H)-one (526 mg, 90%). LCMS: (FA) ES+ 427, 429, 431. 1H NMR (400 MHz, CDCl3) δ: 7.26 (d, J=8.3 Hz, 2H), 7.07 (d, J=8.3 Hz, 2H), 5.41 (d, J=4.1 Hz, 1H), 4.20-4.06 (m, 2H), 3.87 (dd, J=4.6, 4.6 Hz, 4H), 3.52 (dt, J=14.4, 3.9 Hz, 1H), 3.35-3.24 (m, 2H), 3.24-3.10 (m, 2H).

Workup

  1. customReaction
  2. customwas quenched via addition of 10% aqueous sodium thiosulfate solution (30 mL)
  3. additiondiluted with EtOAc (100 mL) and water (10 mL) with sonication
  4. dissolutiondissolution of solids
  5. customThe layers were separated
  6. extractionaqueous layer was extracted 1×EtOAc (50 mL)
  7. washThe combined organic layers were washed 1× brine (10 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-016b4e5a9cd249b1af89081d4b092255
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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