Chlorosuccinimide → HCID 53353296, compound

HRID 2405114Notes

Reaction equation

HRID 2405114 reaction equation
[OH:1][CH2:2][C@@:3]([C:6]1[CH:24]=[CH:23][C:9]([C:10]([NH:12][C:13]2[N:18]=[CH:17][C:16]3[CH:19]=[CH:20][N:21]([CH3:22])[C:15]=3[CH:14]=2)=[O:11])=[CH:8][CH:7]=1)([OH:5])[CH3:4].C1C(=O)N([Cl:32])C(=O)C1>CN(C=O)C>[Cl:32][C:19]1[C:16]2[CH:17]=[N:18][C:13]([NH:12][C:10](=[O:11])[C:9]3[CH:23]=[CH:24][C:6]([C@:3]([OH:5])([CH3:4])[CH2:2][OH:1])=[CH:7][CH:8]=3)=[CH:14][C:15]=2[N:21]([CH3:22])[CH:20]=1

Participants

4

Reactant 2

HCID 31398ChlorosuccinimideHCID 71087510HCID 71087510, compound

Product 1

HCID 53353296HCID 53353296, compoundYield 21.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(R)-4-(1,2-dihydroxypropan-2-yl)-N-(1-methyl-1H-pyrrolo[3,2-c]pyridin-6-yl)benzamide (750 mg, 2.3 mmol) was dissolved in DMF (20 ml) and NCS (310 mg, 2.3 mmol) was added to it. Stirring continued at 50° C. for 3 hours. The mixture was poured into 50 ml ice water and was extracted into ethyl acetate (3×100 ml). Combined organic layers were dried over sodium sulfate and concentrated in vacuo. The crude product was purified by preparatory HPLC (TFA mode, 15-50% ACN in water). Fractions containing the desired mono chlorinated product were combined, concentrated, washed with saturated NaHCO3 and brine, and then extracted into ethyl acetate (2×100 ml). Combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to obtain the title compound (R)—N-(3-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridin-6-yl)-4-(1,2-dihydroxypropan-2-yl)benzamide (18 mg, 0.49 mmol, 21%) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.42 (s, 3H) 3.45 (dd, J=5.81, 2.53 Hz, 2H) 3.78 (s, 2H) 4.74 (t, J=5.81 Hz, 1H) 5.03 (s, 1H) 7.46-7.69 (m, 2H) 8.01 (d, J=8.59 Hz, 2H) 8.34 (d, J=0.76 Hz, 1H) 8.59 (d, J=0.76 Hz, 1H) 10.64 (s, 1H); ESI-MS: m/z 360 (M+H)+; m.p. 210-212° C.

Workup

  1. extractionwas extracted into ethyl acetate (3×100 ml)
  2. dry with materialCombined organic layers were dried over sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by preparatory HPLC (TFA mode, 15-50% ACN in water)
  5. additionFractions containing the desired
  6. concentrationconcentrated
  7. washwashed with saturated NaHCO3 and brine
  8. extractionextracted into ethyl acetate (2×100 ml)
  9. dry with materialCombined organic layers were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f741cd3636774b0ba4a44327d2d1a6a9
Source dataset
uspto-grants-2014_08
Patent number
US08802695B2

Reaction notes

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