Chloride → HCID 67093855, compound

HRID 1630825Notes

Reaction equation

HRID 1630825 reaction equation
O[CH2:2][N:3]1[CH2:6][C:5]([CH3:8])([CH3:7])[C:4]1=[O:9].S(Cl)(Cl)=O.[N:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]2[NH:21][C:22]3[C:27]([CH:28]=2)=[CH:26][C:25]([C:29]#[N:30])=[CH:24][CH:23]=3)[CH:15]=1.[H-].[Na+].[Cl-]>CN(C=O)C.ClCCl>[CH3:7][C:5]1([CH3:8])[CH2:6][N:3]([CH2:2][N:21]2[C:22]3[C:27](=[CH:26][C:25]([C:29]#[N:30])=[CH:24][CH:23]=3)[CH:28]=[C:20]2[C:16]2[CH:15]=[N:14][CH:19]=[CH:18][CH:17]=2)[C:4]1=[O:9]

Participants

8

Reactant 5

HCID 312ChlorideHCID 24386Thionyl ChlorideHCID 24758Sodium hydride2×HCID 445541352-pyridin-3-yl-1H-indole-5-carbonitrileHCID 58215705HCID 58215705, compound

Product 1

HCID 67093855HCID 67093855, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A flask is charged with 1-hydroxymethyl-3,3-dimethyl-azetidin-2-one (0.179 g, 1.317 mmol) and dichloromethane (5 mL), and thionyl chloride (0.63 g, 5.27 mmol) is added. The mixture is stirred at room temperature overnight and concentrated in vacuo to yield an oil, which is redissolved in DMF (0.8 mL). 2-Pyridin-3-yl-1H-indole-5-carbonitrile (Example 8, 0.213 g, 0.922 mmol) is dissolved in DMF (5 mL), cooled to 0° C., and NaH (0.053 g, 1.317 mmol) is added portionwise. After 30 min, the chloride solution is added. After 1 h, NaH (0.027 g, 0.67 mmol) is added and the mixture is stirred overnight. The mixture is quenched with a few drops of water and diluted with methanol and DMSO. The mixture is purified on Xbridge C18 eluting with a 9:1 to 1:9 water-acetonitrile gradient to give 1-(3,3-dimethyl-2-oxo-azetidin-1-ylmethyl)-2-pyridin-3-yl-1H-indole-5-carbonitrile. 1H NMR (400 MHz, CDCl3) δ ppm 1.18 (s, 6H), 2.82 (s, 2H), 5.47 (s, 2H), 6.71 (s, 1H), 7.47-7.51 (m, 1H), 7.56 (dd, J=8.6, 1.5 Hz, 1H), 7.73 (d, J=8.6 Hz, 1H), 7.80-7.83 (m, 1H), 8.01 (d, J=1.5 Hz, 1H), 8.75-8.76 (m, 2H). HRMS (ESI) m/z 331.1558 [(M+H)+ Calcd for C20H19N4O: 331.1559].

Workup

  1. additionis added
  2. concentrationconcentrated in vacuo
  3. customto yield an oil, which
  4. temperaturecooled to 0° C.
  5. waitAfter 30 min
  6. waitAfter 1 h
  7. stirringthe mixture is stirred overnight
  8. customThe mixture is quenched with a few drops of water
  9. additiondiluted with methanol and DMSO
  10. customThe mixture is purified on Xbridge
  11. washC18 eluting with a 9:1 to 1:9 water-acetonitrile gradient

Sources & evidence

ORD record
ord-0dfd85dcaae7418797878aa03336d8fb
Source dataset
uspto-grants-2014_07
Patent number
US08791141B2

Reaction notes

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