4-Methylmorpholine → 2-{2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-N,N-dimethyl-acetamide

HRID 1515677Notes

Reaction equation

HRID 1515677 reaction equation
[CH:1]1([CH2:6][CH:7]([C:18]2[NH:30][C:21]3=[N:22][CH:23]=[C:24]([CH2:26][C:27]([OH:29])=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.[CH3:32][NH:33][CH3:34].CN1CCOCC1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O.C(OCC)(=O)C>[CH:1]1([CH2:6][CH:7]([C:18]2[NH:30][C:21]3=[N:22][CH:23]=[C:24]([CH2:26][C:27]([N:33]([CH3:34])[CH3:32])=[O:29])[CH:25]=[C:20]3[CH:19]=2)[C:8]2[CH:9]=[CH:10][C:11]([S:14]([CH3:17])(=[O:15])=[O:16])=[CH:12][CH:13]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 10473Dimethylamine, hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 67229455{2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-acetic acid

Product 1

HCID 532510832-{2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-N,N-dimethyl-acetamideYield 58.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 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-yl}-acetic acid (75 mg, 0.17 mmol) and dimethylamine hydrochloride (43 mg, 0.53 mmol) in N,N-dimethylformamide (2 mL) and N-methylmorpholine (97 uL, 0.88 mmol) was added 1-hydroxybenzotriazole hydrate (110 mg, 0.81 mmol) followed by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (68 mg, 0.35 mmol) in one portion. The mixture was stirred at 25° C. for 6 h. The mixture was diluted with ethyl acetate (100 mL), washed with a 1 N aqueous sodium bicarbonate solution, 1N 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-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-N,N-dimethyl-acetamide (45 mg, 56%) as a light yellow solid: LC/MS m/e calcd for C25H31N3O3S [M+H]+ 454.61, observed 454.1; 1H NMR (400 MHz, CDCl3) δ ppm 1.18 (m, 2H), 1.48 (m, 2H), 1.56-1.85 (m, 5H, H), 2.10 (m, 1H), 2.23 (m, 1H), 2.99 (s, 3H), 3.04 (s, 3H), 3.10 (s, 3H), 3.81 (s, 2H), 4.29 (t, J=7.8 Hz, 1H), 6.35 (s, 1H), 7.50 (d, J=8.3 Hz, 2H), 7.86 (d, J=8.3 Hz, 2H), 7.96 (s, 1H), 8.02 (s, 1H), 10.99 (br, 1H).

Workup

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

Sources & evidence

ORD record
ord-88c19f93bc8840ea9e655fbab4297c1d
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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