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

HRID 751718Notes

Reaction equation

HRID 751718 reaction equation
[F:1][C:2]1[CH:44]=[CH:43][C:5]([CH2:6][C@H:7]([NH:30][C:31]([C:33]2[NH:42][C:36]3=[CH:37][N:38]=[C:39]([Cl:41])[CH:40]=[C:35]3[CH:34]=2)=[O:32])[C:8]([N:10]2[CH2:15][CH2:14][CH:13]([N:16]([CH3:29])S(C3C=CC=CC=3[N+]([O-])=O)(=O)=O)[CH2:12][CH2:11]2)=[O:9])=[CH:4][CH:3]=1.C1C=CC(S)=CC=1.C(=O)([O-])[O-].[K+].[K+].Cl>C(#N)C.C(OCC)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C@H:7]([NH:30][C:31]([C:33]2[NH:42][C:36]3=[CH:37][N:38]=[C:39]([Cl:41])[CH:40]=[C:35]3[CH:34]=2)=[O:32])[C:8]([N:10]2[CH2:11][CH2:12][CH:13]([NH:16][CH3:29])[CH2:14][CH2:15]2)=[O:9])=[CH:43][CH:44]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7969ThiophenolHCID 11430Potassium CarbonateHCID 597537125-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (1-(S)-(4-fluorobenzyl)-2-{4-[methyl(2-nitrobenzenesulfonyl)amino]piperidin-1-yl}-2-oxoethyl)amide

Product 1

HCID 597535225-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid [1-(S)-(4-fluorobenzyl)-2-(4-methylaminopiperidin-1-yl)-2-oxoethyl]amide

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (1-(S)-(4-fluorobenzyl)-2-{4-[methyl-(2-nitrobenzenesulfonyl)amino]piperidin-1-yl}-2-oxoethyl)amide (Preparation 76, 82 mg, 0.13 mmol) in acetonitrile (6 mL) was added phenylthiol (145 μL, 1.4 mmol) followed by potassium carbonate (230 mg, 1.66 mmol) and the reaction heated to 50° C. for 24 h. To the mixture was added diethyl ether (10 mL) and 1M HCl (15 mL) and stirred for 5 min. The organic layer was separated and washed with 1M HCl (15 mL) before combining the aqueous layers. The solution was basified to pH9 with solid potassium carbonate and extracted with ethyl acetate (2×20 mL). Organic layers were combined, washed with brine (2×20 mL) and dried (MgSO4). Removal of the solvent in vacuo provided the desired product as an off-white powder. m/z (ES+)=458.40 [M+H]+; RT=2.67 min. A small portion of the product (10 mg) was dissolved in methanol (2 mL) and 1M HCl added to bring the solution to pH 1–2. After stirring for 20 min the solvent was removed in vacuo to give the title compound as the hydrochloride salt as a yellow powder. m/z (ES+)=458.38 [M+H]+; RT=2.64 min.

Workup

  1. customThe organic layer was separated
  2. washwashed with 1M HCl (15 mL)
  3. extractionextracted with ethyl acetate (2×20 mL)
  4. washwashed with brine (2×20 mL)
  5. dry with materialdried (MgSO4)
  6. customRemoval of the solvent in vacuo

Sources & evidence

ORD record
ord-f0a34d2268ca4d48aabe17de6ceb6d5b
Source dataset
uspto-grants-2008_07
Patent number
US07405210B2

Reaction notes

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