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

HRID 1515586Notes

Reaction equation

HRID 1515586 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]([OH:26])=O)[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].[CH:28]([NH2:31])([CH3:30])[CH3:29].CN1CCOCC1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>ClCCl.CN(C)C=O.C(OCC)(=O)C>[CH:28]([NH:31][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:3])=[O:4])=[CH:10][CH:9]=3)[CH2:12][CH:13]([CH3:14])[CH3:15])[NH:27][C:19]2=[N:20][CH:21]=1)=[O:26])([CH3:30])[CH3:29]

Participants

9

Reactant 5

HCID 6363IsopropylamineHCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 672298582-[1-(4-methanesulfonyl-phenyl)-3-methyl-butyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid

Product 1

HCID 532502862-[1-(4-methanesulfonyl-phenyl)-3-methyl-butyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid isopropylamideYield 20.2%

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 (200 mg, 0.52 mmol) and isopropylamine (54 μL, 0.62 mmol) in dichloromethane (1 mL), N,N-dimethylformamide (500 μL) and N-methylmorpholine (200 μL, 1.56 mmol) was added 1-hydroxybenzotriazole hydrate (141 mg, 1.04 mmol) followed by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (199 mg, 1.04 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 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 isopropylamide (45 mg, 20%) as a white solid: LC/MS m/e calcd for C23H29N3O3S [M+H]+ 428.57, observed 428.2; 1H NMR (400 MHz, CDCl3) δ ppm 0.94 (d, J=6.7 Hz, 3H), 0.97 (d, J=6.7 Hz, 3H), 1.29 (d, J=6.6 Hz, 6H), 1.49 (m, 1H), 1.96 (m, 1H), 2.08 (m, 1H), 3.03 (s, 3H), 4.24-4.37 (m, 2H), 6.17 (d, J=7.9 Hz, 1H), 6.38 (s, 1H), 7.43 (d, J=8.3 Hz, 2H), 7.84 (d, J=8.3 Hz, 2H), 8.24 (d, J=2.0 Hz, 1H), 8.55 (d, J=2.0 Hz, 1H), 10.31 (br, 0.3H).

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-733b15b2247a43ed803320f76d3b2083
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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