Diethyl Ether → HCID 53354691, compound

HRID 1478920Notes

Reaction equation

HRID 1478920 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.CCOCC>CN(C=O)C.[Cl-].[Na+].O>[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

6

Reactant 3

HCID 3283Diethyl EtherHCID 31398Chlorosuccinimide2×HCID 53354592HCID 53354592, compound

Product 1

HCID 53354691HCID 53354691, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
60 °C

Procedure

In a 200 mL pear flask was added (R)-4-(1,2-dihydroxypropan-2-yl)-N-(1-ethyl-1H-pyrrolo[3,2-c]pyridin-6-yl)benzamide (13, 3.2 g, 7.1 mmol) in anhydrous DMF (45 ml) to give a brown suspension. At room temperature, N-chlorosuccinimide (0.94 g, 7.1 mmol) was added, and the mixture was heated to 60° C. for 4 hours. An additional 0.2 equivalent of N-chlorosuccinimide was added at room temperature. After an additional 1.5 hours of heating at 60° C., the mixture was cooled to room temperature. Brine was added, and the mixture was extracted with ethyl acetate twice. Combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated until a precipitate was formed. Ether was added and the red solid was collected on a fritted filter, while the filtrate was concentrated. The oil was then purified by column chromatography (SiO2, 75-100% EtOAc/hexanes+0.25% MeOH). The product-containing fractions were combined and concentrated. The residue was combined with the red solid collected earlier and the mixture was resuspended in hot EtOAc/methanol mixture. After cooling, the much lighter-colored solid was collected on a fritted-glass filter under nitrogen, and washed with Et2O to remove most of the colored impurities to give the title compound (R)-N-(3-chloro-1-ethyl-1H-pyrrolo[3,2-c]pyridin-6-yl)-4-(1,2-dihydroxypropan-2-yl)benzamide (14, 1.7 g, 64% yield) as a light-pink solid. 1H NMR (DMSO-d6) d: 10.68 (s, 1 H), 8.60 (s, 1 H), 8.38 (s, 1 H), 8.01 (d, J=8.3 Hz, 2 H), 7.69 (s, 1 H), 7.58 (d, J=8.6 Hz, 2 H), 5.05 (s, 1 H), 4.76 (t, J=5.8 Hz, 1 H), 4.19 (q, J=7.2 Hz, 2 H), 3.40-3.50 (m, 2 H), 1.42 (s, 3 H), 1.38 (t, J=7.3 Hz, 3 H); ESI-MS: m/z 374 (M+H)+; m.p. 224.4-225.1° C.

Workup

  1. customto give a brown suspension
  2. temperatureAfter an additional 1.5 hours of heating at 60° C.
  3. temperaturethe mixture was cooled to room temperature
  4. extractionthe mixture was extracted with ethyl acetate twice
  5. washCombined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated until a precipitate
  9. customwas formed
  10. customthe red solid was collected on a fritted filter, while the filtrate
  11. concentrationwas concentrated
  12. customThe oil was then purified by column chromatography (SiO2, 75-100% EtOAc/hexanes+0.25% MeOH)
  13. concentrationconcentrated
  14. customcollected earlier
  15. temperatureAfter cooling
  16. customthe much lighter-colored solid was collected on a fritted-glass
  17. filtrationfilter under nitrogen
  18. washwashed with Et2O
  19. customto remove most of the colored impurities

Sources & evidence

ORD record
ord-d36bd15577fb4b7a8e007c324b7843ff
Source dataset
uspto-grants-2016_08
Patent number
US09403819B2

Reaction notes

Loading…