Water → HCID 53353199, compound

HRID 1478924Notes

Reaction equation

HRID 1478924 reaction equation
[OH:1][C:2]([C:5]1[CH:23]=[CH:22][C:8]([C:9]([NH:11][C:12]2[N:17]=[CH:16][C:15]3[CH:18]=[CH:19][N:20]([CH3:21])[C:14]=3[CH:13]=2)=[O:10])=[CH:7][CH:6]=1)([CH3:4])[CH3:3].[Cl:24]N1C(=O)CCC1=O.O>CN(C=O)C>[Cl:24][C:18]1[C:15]2[CH:16]=[N:17][C:12]([NH:11][C:9](=[O:10])[C:8]3[CH:22]=[CH:23][C:5]([C:2]([OH:1])([CH3:3])[CH3:4])=[CH:6][CH:7]=3)=[CH:13][C:14]=2[N:20]([CH3:21])[CH:19]=1

Participants

5

Reactant 3

HCID 962WaterHCID 31398ChlorosuccinimideHCID 67354559HCID 67354559, compound

Product 1

HCID 53353199HCID 53353199, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

In a 125 ml round bottom flask, 4-(2-hydroxypropan-2-yl)-N-(1-methyl-1H-pyrrolo[3,2-c]pyridin-6-yl)benzamide (2.8 g, 9.05 mmol) was dissolved in DMF (25 ml). To this was added N-chlorosuccinimide (1.5 g, 11 mmol) and the mixture was stirred at 50° C. for 3 hours. The mixture was then poured into 50 ml water and then extracted with ethyl acetate (3×100 ml). Combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by preparatory HPLC (RFA-mode: eluting with 25-55% ACN in water). Fractions containing the desired mono chlorinated product were combined and concentrated. To the residue was added saturated NaHCO3 and the aqueous mixture was extracted with ethyl acetate (2×100 ml). Combined organic layers were dried over sodium sulfate, filtered and concentrated to obtain the title compound (840 mg, 27% yield) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.25-1.26 (m, 1 H) 1.46 (s, 139 H) 3.66-3.86 (m, 3 H) 5.17 (s, 1 H) 7.40-7.69 (m, 3 H) 8.01 (d, J=8.59 Hz, 2 H) 8.34 (s, 1 H) 8.59 (s, 1 H) 10.68 (s, 1 H)

Workup

  1. extractionextracted with ethyl acetate (3×100 ml)
  2. dry with materialCombined organic layers were dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by preparatory HPLC (RFA-mode: eluting with 25-55% ACN in water)
  5. additionFractions containing the desired
  6. concentrationconcentrated
  7. additionTo the residue was added saturated NaHCO3
  8. extractionthe aqueous mixture was extracted with ethyl acetate (2×100 ml)
  9. dry with materialCombined organic layers were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-d09789eb25c14c2b95c78b2541531469
Source dataset
uspto-grants-2016_08
Patent number
US09403819B2

Reaction notes

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