4-Methylmorpholine → 2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methylamide

HRID 1515595Notes

Reaction equation

HRID 1515595 reaction equation
[CH:1]1([CH2:6][CH:7]([C:18]2[NH:29][C:21]3=[N:22][CH:23]=[C:24]([C:26]([OH:28])=O)[CH:25]=[C:20]3[CH:19]=2)[C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.CN.[CH3:33][N:34]1CCOCC1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>ClCCl.CN(C)C=O.C(OCC)(=O)C>[CH3:33][NH:34][C:26]([C:24]1[CH:25]=[C:20]2[CH:19]=[C:18]([CH:7]([C:8]3[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:15])=[O:16])=[CH:10][CH:9]=3)[CH2:6][CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)[NH:29][C:21]2=[N:22][CH:23]=1)=[O:28]

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 6364545Methylamine hydrochlorideHCID 672281212-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid

Product 1

HCID 532504322-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methylamideYield 30.8%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid (prepared as in Example 3, 200 mg, 0.48 mmol) and methylamine hydrochloride (39.4 mg, 0.58 mmol) in dichloromethane (1 mL), N,N-dimethylformamide (500 μL) and N-methylmorpholine (152 μL, 1.45 mmol) was added 1-hydroxybenzotriazole hydrate (132 mg, 0.97 mmol) followed by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (186 mg, 0.97 mmol) in one portion. The mixture was then stirred at 25° C. for 14 h. The mixture was diluted with ethyl acetate (100 mL), washed with a 1 N sodium bicarbonate solution, 1 N aqueous hydrochloric acid solution, brine, dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification using a Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded 2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methylamide (63 mg, 30%) as a light yellow solid: LC/MS m/e calcd for C23H27N3O3S [M+H]+ 426.55, observed 426.4; 1H NMR (400 MHz, CDCl3) δ ppm 1.18 (m, 2H), 1.49 (m, 2H), 1.55-1.84 (m, 5H, H), 2.10 (m, 1H), 2.23 (m, 1H), 3.02 (s, 3H), 3.07 (d, J=4.8 Hz, 3H), 4.23 (t, J=8.0 Hz, 1H), 6.36 (q, J=4.8 Hz, 1H), 6.42 (s, 1H), 7.40 (d, J=8.4 Hz, 2H), 7.81 (d, J=8.4 Hz, 2H), 8.21 (d, J=2.1 Hz, 1H), 8.49 (d, J=2.1 Hz, 1H), 10.89 (br. s., 1H).

Workup

  1. washwashed with a 1 N sodium bicarbonate solution, 1 N aqueous hydrochloric acid solution, brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customPurification

Sources & evidence

ORD record
ord-7679a1d599c844a38cd30009a820c94e
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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