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

HRID 1515717Notes

Reaction equation

HRID 1515717 reaction equation
C[O:2][C:3]([C:5]1[CH:6]=[C:7]2[CH:13]=[C:12]([C@@H:14]([C:21]3[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:23][CH:22]=3)[CH2:15][CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[NH:11][C:8]2=[N:9][CH:10]=1)=[O:4].Cl>O1CCCC1.[OH-].[Na+].C(OCC)(=O)C>[CH:16]1([CH2:15][C@@H:14]([C:12]2[NH:11][C:8]3=[N:9][CH:10]=[C:5]([C:3]([OH:4])=[O:2])[CH:6]=[C:7]3[CH:13]=2)[C:21]2[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:23][CH:22]=2)[CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 532514082-[2-cyclopentyl-1(R)-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methyl ester

Product 1

HCID 583052562-[2-cyclopentyl-1(R)-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acidYield 86.6%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 2-[2-cyclopentyl-1(R)-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methyl ester (prepared as in Example 55, 610 mg, 1.43 mmol) in tetrahydrofuran (8 mL) and 10% aqueous sodium hydroxide solution (3 mL) was heated at 70° C. for 10 h. The mixture was neutralized with a 3N aqueous hydrochloric acid solution, diluted with ethyl acetate (150 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to afford 2-[2-cyclopentyl-1(R)-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid (510 mg, 86.6%, 93% ee) as a light yellow solid which was further separated by Agilent high performance liquid chromatography (chiral column: Daicel OJ-H, 250 mm×20 mm i. d., 5 μm-particle size, temperature: 25° C., flow rate of 15 mL/min, 30% ethanol/hexanes as mobile phase and UV detection: 214 and 254 nm) to afford two pure enantiomers. The first peak, 2-[2-cyclopentyl-1(R)-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid (220 mg) was isolated as a light yellow solid: LC/MS m/e calcd for C22H24N2O4S [M+H]+ 413.51, observed 412.9; 1H NMR (400 MHz, CD3OD) δ ppm 8.73 (br. s., 1H), 8.47 (d, J=1.5 Hz, 1H), 8.03 (br. s., 1H), 7.83-7.87 (m, J=8.3 Hz, 2H), 7.53-7.58 (m, J=8.3 Hz, 2H), 6.48 (s, 1H), 4.28 (t, J=7.8 Hz, 1H), 3.04 (s, 3H), 2.20-2.28 (m, 1H), 2.04-2.12 (m, 1H), 1.55-1.82 (m, 5H), 1.38-1.51 (m, 2H), 1.05-1.26 (m, 2H).

Workup

  1. washwashed with brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f01237007b494849bfb6299fd744e3ac
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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