Chlorosuccinimide → HCID 53353294, compound

HRID 2405113Notes

Reaction equation

HRID 2405113 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 67355741HCID 67355741, compound

Product 1

HCID 53353294HCID 53353294, compoundYield 16%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

(S)-4-(1,2-dihydroxypropan-2-yl)-N-(1-methyl-1H-pyrrolo[3,2-c]pyridin-6-yl)benzamide (650 mg, 2.0 mmol) was dissolved in DMF (25 ml) and NCS (270 mg, 2.0 mmol) was added to the mixture, which was stirred at 50° C. for 16 hours. The mixture was then 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 (S)—N-(3-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridin-6-yl)-4-(1,2-dihydroxypropan-2-yl)benzamide (120 mg, 0.32 mmol, 16%) as a brown solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.43 (s, 2H) 2.43-2.64 (m, 1H) 3.46 (dd, J=5.56, 2.53 Hz, 2H) 3.69-3.84 (m, 2H) 4.76 (t, J=5.81 Hz, 1H) 5.04 (s, 1H) 7.40-7.67 (m, 2H) 8.02 (d, J=8.59 Hz, 1H) 8.21-8.40 (m, 1H) 8.59 (s, 1H) 10.65 (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-d1b1daab666b48318f4f3e39180b6905
Source dataset
uspto-grants-2014_08
Patent number
US08802695B2

Reaction notes

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