Diisopropylethylamine → N-((1S,3R,4S)-3-ethyl-4-(5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)cyclopentyl)cyclopropanesulfonamide

HRID 1969816Notes

Reaction equation

HRID 1969816 reaction equation
Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][N:5]=[C:4]2[NH:11][CH:12]=[CH:13][C:3]=12.CCN(C(C)C)C(C)C.[NH2:23][C@@H:24]1[C@H:28]([CH2:29][CH3:30])[CH2:27][C@H:26]([NH:31][S:32]([CH:35]2[CH2:37][CH2:36]2)(=[O:34])=[O:33])[CH2:25]1.Cl>CN(C=O)C.CCOC(C)=O>[CH2:29]([C@H:28]1[C@@H:24]([NH:23][C:2]2[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][N:5]=[C:4]3[NH:11][CH:12]=[CH:13][C:3]=23)[CH2:25][C@@H:26]([NH:31][S:32]([CH:35]2[CH2:37][CH2:36]2)(=[O:33])=[O:34])[CH2:27]1)[CH3:30]

Participants

6

Reactant 3

HCID 81531Diisopropylethylamine3×HCID 585572594-Chloro-5-nitro-1H-pyrrolo[2,3-b]pyridineHCID 67997976N-((1S,3S,4R)-3-amino-4-ethylcyclopentyl)cyclopropanesulfonamide hydrochloride3×

Product 1

HCID 67999320N-((1S,3R,4S)-3-ethyl-4-(5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)cyclopentyl)cyclopropanesulfonamideYield 42.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 4-chloro-5-nitro-1H-pyrrolo[2,3-b]pyridine (0.158 g, 0.800 mmol) in DMF (8.7 mL) was added DIEA (0.419 mL, 2.399 mmol) and N-((1S,3S,4R)-3-amino-4-ethylcyclopentyl)cyclopropanesulfonamide•hydrochloride (0.215 g, 0.800 mmol). The reaction mixture was heated at about 60° C. for about 60 h. The temperature was increased to about 70° C. for about 2 h then DIEA (0.279 mL, 1.599 mmol) and N-((1S,3S,4R)-3-amino-4-ethylcyclopentyl)cyclopropanesulfonamide hydrochloride (0.093 g, 0.346 mmol) were added. The reaction mixture was heated at about 70° C. for about 2 h. Additional N-((1S,3S,4R)-3-amino-4-ethylcyclopentyl)cyclopropanesulfonamide hydrochloride (0.060 g, 0.223 mmol) was added and the reaction mixture was heated at about 70° C. for about 30 min. Additional DIEA (0.279 mL, 1.599 mmol) was added and the reaction mixture was heated at about 70° C. for about 1 h. The reaction mixture was cooled to ambient temperature and concd in vacuo. The residue was dissolved in EtOAc (25 mL) and washed with water (20 mL). The organic layer was separated, dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The crude material was purified by silica gel chromatography eluting with a gradient of 0-5% MeOH in DCM to give N-((1S,3R,4S)-3-ethyl-4-(5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)cyclopentyl)cyclopropanesulfonamide (0.134 g, 41%) as an orange solid: LC/MS (Table 1, Method n) Rt=0.66 min; MS m/z 394 (M+H)+.

Workup

  1. temperatureThe temperature was increased to about 70° C. for about 2 h
  2. temperatureThe reaction mixture was heated at about 70° C. for about 2 h
  3. temperaturethe reaction mixture was heated at about 70° C. for about 30 min
  4. temperaturethe reaction mixture was heated at about 70° C. for about 1 h
  5. temperatureThe reaction mixture was cooled to ambient temperature
  6. washwashed with water (20 mL)
  7. customThe organic layer was separated
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. customThe crude material was purified by silica gel chromatography
  11. washeluting with a gradient of 0-5% MeOH in DCM

Sources & evidence

ORD record
ord-f561129ad5fd4ef18d7309c3d31c3bf2
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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