Chlorosuccinimide → HCID 53353201, compound

HRID 2405110Notes

Reaction equation

HRID 2405110 reaction equation
[OH:1][CH2:2][C@:3]([C:6]1[CH:25]=[CH:24][C:9]([C:10]([NH:12][C:13]2[N:18]=[CH:17][C:16]3[CH:19]=[CH:20][N:21]([CH2:22][CH3:23])[C:15]=3[CH:14]=2)=[O:11])=[CH:8][CH:7]=1)([OH:5])[CH3:4].[Cl:26]N1C(=O)CCC1=O>CN(C=O)C>[Cl:26][C:19]1[C:16]2[CH:17]=[N:18][C:13]([NH:12][C:10](=[O:11])[C:9]3[CH:24]=[CH:25][C:6]([C@@:3]([OH:5])([CH3:4])[CH2:2][OH:1])=[CH:7][CH:8]=3)=[CH:14][C:15]=2[N:21]([CH2:22][CH3:23])[CH:20]=1

Participants

4

Reactant 2

HCID 31398Chlorosuccinimide2×HCID 71087863HCID 71087863, compound

Product 1

HCID 53353201HCID 53353201, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

In a 50 mL pear flask was added (S)-4-(1,2-dihydroxypropan-2-yl)-N-(1-ethyl-1H-pyrrolo[3,2-c]pyridin-6-yl)benzamide (92 mg, 0.27 mmol) in DMF (2 ml) to give a solution. At room temperature 1-chloropyrrolidine-2,5-dione (36 mg, 0.27 mmol) was added, and the mixture was heated to 60° C. for 4 hours, at which point the reaction seemed to have stalled. An additional 0.2 equivalence of 1-chloropyrrolidine-2,5-dione was added, and the mixture was heated to 60° C. for another hour. The mixture was then cooled, and partitioned between brine and EtOAc. The aqueous layer was further extracted with EtOAc, and the organic layers were combined, washed with brine, dried, filtered and concentrated in vacuo. The residue was then triturated with hot EtOAc, and the resulting precipitate was collected on a fritted-glass funnel. The collected solid was then recrystallized from EtOH to give the product (S)—N-(3-chloro-1-ethyl-1H-pyrrolo[3,2-c]pyridin-6-yl)-4-(1,2-dihydroxypropan-2-yl)benzamide (23 mg, 0.062 mmol, 22% yield) as a pink solid. 1H NMR (DMSO-d6) δ 10.68 (s, 1H), 8.60 (s, 1H), 8.37 (s, 1H), 8.02 (s, 2H), 7.69 (s, 1H), 7.59 (s, 2H), 5.05 (s, 1H), 4.76 (t, J=5.8 Hz, 1H), 4.19 (q, J=7.1 Hz, 2H), 3.40-3.50 (m, 2H), 1.34-1.45 (m, 6H); m.p. 223.0-223.9° C.

Workup

  1. customto give a solution
  2. temperaturethe mixture was heated to 60° C. for another hour
  3. temperatureThe mixture was then cooled
  4. custompartitioned between brine and EtOAc
  5. extractionThe aqueous layer was further extracted with EtOAc
  6. washwashed with brine
  7. customdried
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was then triturated with hot EtOAc
  11. customthe resulting precipitate was collected on a fritted-glass funnel
  12. customThe collected solid was then recrystallized from EtOH

Sources & evidence

ORD record
ord-71f4e8c10b134281ba3663c8a65bda3d
Source dataset
uspto-grants-2014_08
Patent number
US08802695B2

Reaction notes

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