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

HRID 1515587Notes

Reaction equation

HRID 1515587 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]([C:16]2[NH:27][C:19]3=[N:20][CH:21]=[C:22]([C:24](O)=[O:25])[CH:23]=[C:18]3[CH:17]=2)[CH2:12][CH:13]([CH3:15])[CH3:14])=[CH:7][CH:6]=1)(=[O:4])=[O:3].Cl.CN.[CH3:31][N:32]1CCOCC1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>ClCCl.CN(C)C=O.C(OCC)(=O)C>[CH3:31][NH:32][C:24]([C:22]1[CH:23]=[C:18]2[CH:17]=[C:16]([CH:11]([C:8]3[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:10][CH:9]=3)[CH2:12][CH:13]([CH3:15])[CH3:14])[NH:27][C:19]2=[N:20][CH:21]=1)=[O:25]

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 6364545Methylamine hydrochlorideHCID 672298582-[1-(4-methanesulfonyl-phenyl)-3-methyl-butyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid

Product 1

HCID 532504302-[1-(4-methanesulfonyl-phenyl)-3-methyl-butyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methylamideYield 12%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 2-[1-(4-methanesulfonyl-phenyl)-3-methyl-butyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid (prepared as in Example 1, 432 mg, 1.12 mmol) and methylamine hydrochloride (151 mg, 2.23 mmol) in dichloromethane (8 mL), N,N-dimethylformamide (2 mL) and N-methylmorpholine (370 μL, 3.36 mmol) was added 1-hydroxybenzotriazole hydrate (380 mg, 2.8 mmol) followed by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (540 mg, 2.8 mmol) in one portion. The mixture was then stirred at 25° C. for 14 h. The mixture was diluted with ethyl acetate (200 mL), washed with a 1 N aqueous 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-[1-(4-methanesulfonyl-phenyl)-3-methyl-butyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methylamide (53 mg, 12%) as a white solid: LC/MS m/e calcd for C21H26N3O3S [M+H]+ 400.52, observed 400.2; 1H NMR (400 MHz, CDCl3) δ ppm 0.97 (d, J=6.9 Hz, 3H), 0.99 (d, J=6.9 Hz, 3H), 1.52 (m, 1H), 1.96 (m, 1H), 2.11 (m, 1H), 3.04 (s, 3H), 3.08 (d, J=4.4 Hz, 3H), 4.31 (m, 1H), 6.35 (m, 1H), 6.42 (s, 1H), 7.41 (d, J=8.3 Hz, 2H), 7.82 (d, J=8.3 Hz, 2H), 8.25 (s, 1H), 8.50 (s, 1H), 10.84 (br. s., 1H).

Workup

  1. washwashed with a 1 N aqueous 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-e35a253a2fc044e5a3425f8e2ae73a58
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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