Sodium Iodide → 9-Benzenesulfonyl-3-bromo-5-{1-[2-(tetrahydropyran-2-yloxy)-ethyl]-piperidin-4-yloxy}-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 60329Notes

Reaction equation

HRID 60329 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3[CH:15]=[N:16][C:17]([C:26]#[N:27])=[C:18]([O:19][CH:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)[C:13]=3[C:12]3[CH:28]=[C:29]([Br:32])[CH:30]=[N:31][C:11]2=3)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[I-].[Na+].Br[CH2:36][CH2:37][O:38][CH:39]1[CH2:44][CH2:43][CH2:42][CH2:41][O:40]1>C(#N)C>[C:1]1([S:7]([N:10]2[C:14]3[CH:15]=[N:16][C:17]([C:26]#[N:27])=[C:18]([O:19][CH:20]4[CH2:25][CH2:24][N:23]([CH2:36][CH2:37][O:38][CH:39]5[CH2:44][CH2:43][CH2:42][CH2:41][O:40]5)[CH2:22][CH2:21]4)[C:13]=3[C:12]3[CH:28]=[C:29]([Br:32])[CH:30]=[N:31][C:11]2=3)(=[O:8])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyranHCID 670274629-benzenesulfonyl-3-bromo-5-(piperidin-4-yloxy)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

Product 1

HCID 672473949-Benzenesulfonyl-3-bromo-5-{1-[2-(tetrahydropyran-2-yloxy)-ethyl]-piperidin-4-yloxy}-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrileYield 33.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of 9-benzenesulfonyl-3-bromo-5-(piperidin-4-yloxy)-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (789 mg, 1.54 mmol) in acetonitrile (50 mL) was added sodium iodide (46 mg, 0.31 mmol) and the resultant suspension sonicated for 5 minutes. 2-(2-Bromoethoxy)tetrahydropyran (483 mg, 2.31 mmol) was added and the reaction mixture was heated to 50° C. for 48 hours. The resultant residue was concentrated in-vacuo then dissolved in dichloromethane, diluted with 1N aqueous sodium carbonate (50 mL) and extracted with dichloromethane (3×50 mL). The combined organic layer was dried (Na2SO4), filtered, evaporated in-vacuo and the resultant residue purified by flash chromatography (silica, 40 g column, ISCO, 0-30% ethyl acetate in dichloromethane) to afford the title compound as a pale yellow solid (330 mg, 33%). 1H NMR (300 MHz, CDCl3): 9.54 (s, 1H), 8.76 (d, J=2.3 Hz, 1H), 8.65 (d, J=2.3 Hz, 1H), 8.23-8.22 (m, 2H), 7.64-7.64 (m, 1H), 7.53-7.50 (m, 2H), 5.13-5.11 (m, 1H), 4.59 (t, J=3.5 Hz, 1H), 3.87-3.86 (m, 2H), 3.54-3.52 (m, 2H), 2.99 (d, J=11.6 Hz, 2H), 2.67 (t, J=6.0 Hz, 2H), 2.35 (t, J=11.3 Hz, 2H), 2.22 (d, J=12.3 Hz, 2H), 2.03-1.99 (m, 2H), 1.87-1.47 (m, 6H).

Workup

  1. concentrationThe resultant residue was concentrated in-vacuo
  2. dissolutionthen dissolved in dichloromethane
  3. additiondiluted with 1N aqueous sodium carbonate (50 mL)
  4. extractionextracted with dichloromethane (3×50 mL)
  5. dry with materialThe combined organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in-vacuo
  8. customthe resultant residue purified by flash chromatography (silica, 40 g column, ISCO, 0-30% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-d5dc920f8ca240e98758a40b83335b8a
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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