5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid → 5-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid [1-(S)-(4-fluorobenzyl)-2-(4-hydroxypiperidin-1-yl)-2-oxoethyl]amide

HRID 1693420Notes

Reaction equation

HRID 1693420 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[CH:10]=[C:9]([C:11]([OH:13])=O)[NH:8][C:5]2=[CH:6][N:7]=1.Cl.[NH2:15][C@@H:16]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=1)[C:17]([N:19]1[CH2:24][CH2:23][CH:22]([OH:25])[CH2:21][CH2:20]1)=[O:18]>>[F:33][C:30]1[CH:31]=[CH:32][C:27]([CH2:26][C@H:16]([NH:15][C:11]([C:9]2[NH:8][C:5]3=[CH:6][N:7]=[C:2]([Cl:1])[CH:3]=[C:4]3[CH:10]=2)=[O:13])[C:17]([N:19]2[CH2:20][CH2:21][CH:22]([OH:25])[CH2:23][CH2:24]2)=[O:18])=[CH:28][CH:29]=1

Participants

3

Reactant 2

HCID 446307045-chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acidHCID 67278381(S)-2-Amino-3-(4-fluoro-phenyl)-1-(4-hydroxy-piperidin-1-yl)-propan-1-one hydrochloride

Product 1

HCID 116986775-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid [1-(S)-(4-fluorobenzyl)-2-(4-hydroxypiperidin-1-yl)-2-oxoethyl]amide

Procedure

Route A: To a solution of 2-(S)-[(5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carbonyl)amino]-3-(4-fluorophenyl)propionic acid (EXAMPLE 228, 1.4 g, 3.87 mmol) in DMF (35 mL) was added HATU (1.77 g, 4.64 mmol) and the reaction stirred for 10 min. 4-Hydroxypiperidine (0.43 g, 4.26 mmol) was added, followed by DIPEA (0.8 mL, 4.64 mmol) and the reaction stirred at rt for 16 h. Solvent was removed in vacuo and the crude material partitioned between ethyl acetate (50 mL) and water (50 mL). The organics were washed with sodium bicarbonate (2×30 mL) and brine (2×30 mL), dried (MgSO4) and the solvent removed in vacuo. Purification by column chromatography (SiO2, 96:4 dichloromethane/methanol) gave the title compound. m/z (ES+)=445.15 [M+H]+; RT=3.24 min. Route B: The title compound was prepared as outlined in EXAMPLE 1 from 5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (Preparation 18) and 2-(S)-amino-3-(4-fluorophenyl)-1-(4-hydroxypiperidin-1-yl)propan-1-one hydrochloride (Preparation 20). The product was purified by chromatography on silica gel eluting with methanol/dichloromethane (1:19) to give the title compound as a pale yellow solid. δH (CD3OD): 1.08-1.19 (0.5H, m), 1.29-1.51 (1.5H, m), 1.54-1.62 (0.5H, m), 1.73-1.84 (1.5H, m), 3.06-3.36 (4H, m), 3.67-3.95 (2.5H, m), 4.03-4.10 (0.5H, m), 5.32 (1H, t), 6.97-7.04 (2H, m), 7.14 (1H, s), 7.26-7.33 (2H, m), 7.66 (1H, s), 8.55 (1H, s); m/z (ES+)=445 [M+H]+; RT=3.27 min.

Workup

  1. customRoute B: The title compound was prepared
  2. customThe product was purified by chromatography on silica gel eluting with methanol/dichloromethane (1:19)

Sources & evidence

ORD record
ord-b5ea4e8b03684b098f19dcdd68542e13
Source dataset
uspto-grants-2012_04
Patent number
US08158622B2

Reaction notes

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