p-Toluenesulfonic acid → 9-Benzenesulfonyl-3-bromo-5-[1-(2-hydroxyethyl)-piperidin-4-yloxy]-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 60330Notes

Reaction equation

HRID 60330 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3[CH:15]=[N:16][C:17]([C:35]#[N:36])=[C:18]([O:19][CH:20]4[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][O:28]C5CCCCO5)[CH2:22][CH2:21]4)[C:13]=3[C:12]3[CH:37]=[C:38]([Br:41])[CH:39]=[N:40][C:11]2=3)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC1C=CC(S(O)(=O)=O)=CC=1>ClCCl.CO>[C:1]1([S:7]([N:10]2[C:14]3[CH:15]=[N:16][C:17]([C:35]#[N:36])=[C:18]([O:19][CH:20]4[CH2:21][CH2:22][N:23]([CH2:26][CH2:27][OH:28])[CH2:24][CH2:25]4)[C:13]=3[C:12]3[CH:37]=[C:38]([Br:41])[CH:39]=[N:40][C:11]2=3)(=[O:8])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 672473949-Benzenesulfonyl-3-bromo-5-{1-[2-(tetrahydropyran-2-yloxy)-ethyl]-piperidin-4-yloxy}-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

Product 1

HCID 672483089-Benzenesulfonyl-3-bromo-5-[1-(2-hydroxyethyl)-piperidin-4-yloxy]-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrileYield 107.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 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 (330 mg, 0.52 mmol) in dichloromethane (5 mL) and methanol (10 mL) was added tosic acid monhydrate (100 mg, 0.52 mmol) and the reaction mixture heated to 40° C. for 4 hours then concentrated in-vacuo. The resultant residue was was taken up in dichloromethane, diluted with saturated aqueous sodium bicarbonate (20 mL) and extracted with dichloromethane (3×20 mL). The combined organic layer was dried (Na2SO4), filtered, evaporated in-vacuo to afford the crude title compound as a pale yellow solid (312 mg) which was used without purification. 1H NMR (300 MHz, CDCl3): 9.56 (s, 1H), 8.77 (d, J=2.3 Hz, 1H), 8.63 (d, J=2.3 Hz, 1H), 8.23-8.22 (m, 2H), 7.64-7.63 (m, 1H), 7.52-7.51 (m, 2H), 5.16-5.14 (m, 1H), 3.65 (t, J=5.3 Hz, 2H), 2.96 (m, J=11.5 Hz, 2H), 2.61 (t, J=5.3 Hz, 2H), 2.39 (t, J=11.3 Hz, 2H), 2.25 (m, J=12.5 Hz, 2H), 2.03-2.01 (m, 2H).

Workup

  1. concentrationthen concentrated in-vacuo
  2. additiondiluted with saturated aqueous sodium bicarbonate (20 mL)
  3. extractionextracted with dichloromethane (3×20 mL)
  4. dry with materialThe combined organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated in-vacuo

Sources & evidence

ORD record
ord-eed606ebe06d4d488a2d5f9447aba5c8
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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