Potassium Iodide → N-((1S,3R,4S)-3-ethyl-4-(7-tosyl-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-h][1,6]naphthyridin-1-yl)cyclopentyl)cyclopropanesulfonamide

HRID 1969876Notes

Reaction equation

HRID 1969876 reaction equation
Cl[C:2]1[C:7]([CH2:8][CH2:9][CH2:10][NH:11][C@@H:12]2[C@H:16]([CH2:17][CH3:18])[CH2:15][C@H:14]([NH:19][S:20]([CH:23]3[CH2:25][CH2:24]3)(=[O:22])=[O:21])[CH2:13]2)=[CH:6][N:5]=[C:4]2[N:26]([S:29]([C:32]3[CH:38]=[CH:37][C:35]([CH3:36])=[CH:34][CH:33]=3)(=[O:31])=[O:30])[CH:27]=[CH:28][C:3]=12.CCN(C(C)C)C(C)C.[I-].[K+]>C(O)CC>[CH2:17]([C@H:16]1[C@@H:12]([N:11]2[C:2]3[C:7](=[CH:6][N:5]=[C:4]4[N:26]([S:29]([C:32]5[CH:38]=[CH:37][C:35]([CH3:36])=[CH:34][CH:33]=5)(=[O:31])=[O:30])[CH:27]=[CH:28][C:3]4=3)[CH2:8][CH2:9][CH2:10]2)[CH2:13][C@@H:14]([NH:19][S:20]([CH:23]2[CH2:25][CH2:24]2)(=[O:22])=[O:21])[CH2:15]1)[CH3:18]

Participants

5

Reactant 3

HCID 4875Potassium IodideHCID 81531DiisopropylethylamineHCID 58557549N-((1S,3S,4R)-3-(3-(4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)propylamino)-4-ethylcyclopentyl)cyclopropanesulfonamide

Product 1

HCID 58557285N-((1S,3R,4S)-3-ethyl-4-(7-tosyl-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-h][1,6]naphthyridin-1-yl)cyclopentyl)cyclopropanesulfonamideYield 27%

Reagents, catalysts & solvents 1

HCID 10311-PropanolSolvent

Conditions

Temperature
150 °C

Procedure

A microwave vial was charged with a solution of N-((1S,3S,4R)-3-(3-(4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)propylamino)-4-ethylcyclopentyl)cyclopropanesulfonamide (0.200 g, 0.345 mmol) in 1-propanol (1.70 mL). DIEA (0.180 mL, 1.04 mmol) and potassium iodide (0.057 g, 0.345 mmol) were added and the reaction mixture was heated in a Biotage® microwave at about 150° C. for about 30 min. The reaction was resubmitted to microwave heating at about 180° C. for about 1 h. The reaction was resubmitted to microwave heating at about 180° C. for about 10 h. The reaction mixture was transferred to a round bottom flask and silica gel (about 1 g) was added. The solvent was removed under reduced pressure and the resulting silica gel mixture was purified by silica gel chromatography eluting with a gradient of 0-10% MeOH in DCM to give N-((1S,3R,4S)-3-ethyl-4-(7-tosyl-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-h][1,6]naphthyridin-1-yl)cyclopentyl)cyclopropanesulfonamide (0.050 g, 27%) as a yellow foam: LC/MS (Table 1, Method b) Rt=2.52 min; MS m/z: 543 (M+H)+.

Workup

  1. temperatureto microwave heating at about 180° C. for about 1 h
  2. temperatureto microwave heating at about 180° C. for about 10 h
  3. customThe reaction mixture was transferred to a round bottom flask
  4. additionsilica gel (about 1 g) was added
  5. customThe solvent was removed under reduced pressure
  6. customthe resulting silica gel mixture was purified by silica gel chromatography
  7. washeluting with a gradient of 0-10% MeOH in DCM

Sources & evidence

ORD record
ord-51c387ae45464bd6b4e3b4f9d941cf1b
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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