Ethanolamine → 2-[2-cyclopentyl-1-(6-methanesulfonyl-pyridin-3-yl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid(2-hydroxy-ethyl)-amide

HRID 1515730Notes

Reaction equation

HRID 1515730 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:9]=[N:10][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:12][CH:13]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:30][CH2:31][CH2:32][OH:33].CN1CCOCC1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>ClCCl.CN(C)C=O.C(OCC)(=O)C>[OH:33][CH2:32][CH2:31][NH:30][C:26]([C:24]1[CH:25]=[C:20]2[CH:19]=[C:18]([CH:7]([C:8]3[CH:9]=[N:10][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:12][CH:13]=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 700EthanolamineHCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 672292222-[2-cyclopentyl-1-(6-methanesulfonyl-pyridin-3-yl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid

Product 1

HCID 532514112-[2-cyclopentyl-1-(6-methanesulfonyl-pyridin-3-yl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid(2-hydroxy-ethyl)-amideYield 34.6%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 2-[2-cyclopentyl-1-(6-methanesulfonyl-pyridin-3-yl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid (80 mg, 0.19 mmol) and 2-amino-ethanol (14 uL, 0.23 mmol) in dichloromethane (1 mL), N,N-dimethylformamide (1 mL) and N-methylmorpholine (60 uL, 0.58 mmol) was added 1-hydroxybenzotriazole hydrate (54 mg, 0.39 mmol), followed by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (75 mg, 0.39 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-(6-methanesulfonyl-pyridin-3-yl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid(2-hydroxy-ethyl)-amide (30 mg, 34%) as a white solid: LC/MS m/e calcd for C23H28N4O4S [M+H]+ 456.57, observed 457.0; 1H NMR (400 MHz, CDCl3) δ ppm 1.17 (m, 2H), 1.47 (m, 2H), 1.55-1.84 (m, 5H, H), 2.08 (m, 1H), 2.24 (m, 1H), 3.20 (s, 3H), 3.60 (m, 2H), 3.80 (m, 2H), 4.26 (m, 1H), 6.37 (s, 1H), 7.61 (br, 1 H), 7.85 (br, 1H), 7.97 (m, 1H), 8.29 (m, 1H), 8.59 (br. s., 1H), 8.63 (s, 1H), 11.01 (br, 0.2H).

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-f376df6c8de94986abafc9e031b6fd11
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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