Potassium Iodide → Ammonium Acetate

HRID 1969879Notes

Reaction equation

HRID 1969879 reaction equation
Cl[C:2]1[C:7]([CH2:8][CH2:9][NH:10][C@@H:11]2[C@H:15]([CH2:16][CH3:17])[CH2:14][C@H:13]([NH:18][S:19]([CH:22]3[CH2:24][CH2:23]3)(=[O:21])=[O:20])[CH2:12]2)=[CH:6][N:5]=[C:4]2[N:25](S(C3C=CC(C)=CC=3)(=O)=O)[CH:26]=[CH:27][C:3]=12.CC[N:40](C(C)C)C(C)C.[I-].[K+].CC[O:51][C:52]([CH3:54])=[O:53]>C(O)CC.O>[N:10]1([C@@H:11]2[C@H:15]([CH2:16][CH3:17])[CH2:14][C@H:13]([NH:18][S:19]([CH:22]3[CH2:23][CH2:24]3)(=[O:20])=[O:21])[CH2:12]2)[C:2]2=[C:3]3[CH:27]=[CH:26][NH:25][C:4]3=[N:5][CH:6]=[C:7]2[CH2:8][CH2:9]1.[C:52]([O-:53])(=[O:51])[CH3:54].[NH4+:40]

Participants

8

Reactant 4

HCID 4875Potassium IodideHCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 67998567HCID 67998567, compound

Product 2

HCID 517165Ammonium AcetateHCID 53257641HCID 53257641, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 10311-PropanolSolvent

Conditions

Temperature
180 °C

Procedure

A microwave vial was charged with a solution of N-((1S,3S,4R)-3-(2-(4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)ethylamino)-4-ethylcyclopentyl)cyclopropanesulfonamide (0.350 g, 0.619 mmol) in 1-propanol (3.2 mL). DIPEA (0.324 mL, 1.86 mmol) and potassium iodide (0.154 g, 0.929 mmol) were added and the reaction was heated in a Biotage® microwave for about 10 h at about 180° C. EtOAc and water (10 mL each) were added to the reaction mixture and the layers were separated. The aqueous phase was extracted with EtOAc (2×10 mL). The combined organics were dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with a gradient of 0-100% DCM/MeOH/Et2NH (950/45/5) in DCM and the solvent was removed under reduced pressure. The solid was further purified by preparative HPLC (Table 1, Method w) to give to give N-((1S,3S,4R)-3-(2,3-dihydrodipyrrolo[2,3-b:2′,3′-d]pyridin-1(6H)-yl)-4-ethylcyclopentyl)cyclopropanesulfonamide with 30 mol % ammonium acetate as an excipient (0.099 g, 38%) as a white solid: LC/MS (Table 1, Method a) Rt=1.70 min; MS m/z: 375 (M+H)+.

Workup

  1. customthe layers were separated
  2. extractionThe aqueous phase was extracted with EtOAc (2×10 mL)
  3. dry with materialThe combined organics were dried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with a gradient of 0-100% DCM/MeOH/Et2NH (950/45/5) in DCM
  8. customthe solvent was removed under reduced pressure
  9. customThe solid was further purified by preparative HPLC (Table 1, Method w)
  10. customto give

Sources & evidence

ORD record
ord-98a4cf646b8b4c1eb4bdbc73e238642d
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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