Hydrochloric Acid → 1-{2-[(5-chloropyridin-2-yl)amino]-2-oxoethyl}-5-(2-methoxyethoxy)-N-[1-(propan-2-yl)piperidin-4-yl]-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

HRID 2250445Notes

Reaction equation

HRID 2250445 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([NH:10][C:11]([C:13]2[NH:26][C:16]3=[CH:17][N:18]=[C:19]([O:21][CH2:22][CH2:23][O:24][CH3:25])[CH:20]=[C:15]3[CH:14]=2)=[O:12])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].CN(C=O)C.Br[CH2:33][C:34]([NH:36][C:37]1[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][N:38]=1)=[O:35].Cl>O.CC#N>[CH:1]([N:4]1[CH2:5][CH2:6][CH:7]([NH:10][C:11]([C:13]2[N:26]([CH2:33][C:34](=[O:35])[NH:36][C:37]3[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][N:38]=3)[C:16]3=[CH:17][N:18]=[C:19]([O:21][CH2:22][CH2:23][O:24][CH3:25])[CH:20]=[C:15]3[CH:14]=2)=[O:12])[CH2:8][CH2:9]1)([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 34211102-Bromo-N-(5-chloro-2-pyridinyl)acetamideHCID 865958665-(2-Methoxy-ethoxy)-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide

Product 1

HCID 533163881-{2-[(5-chloropyridin-2-yl)amino]-2-oxoethyl}-5-(2-methoxyethoxy)-N-[1-(propan-2-yl)piperidin-4-yl]-1H-pyrrolo[2,3-c]pyridine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

To a solution of 461 mg (1.27 mmol) ) 5-(2-Methoxy-ethoxy)-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide in 20 mL absolute DMF 46 mg (1.91 mmol) NaH (96%) were added in an argon atmosphere. The mixture was stirred for 15 min. at room temperature. 479 mg (1.91 mmol) 2-Bromo-N-(5-chloro-pyridin-2-yl)-acetamide were added and the mixture stirred for 3 h at room temperature. The solvent was removed in vacuo, the residue dissolved in CH2Cl2 and the CH2Cl2 phase washed with H2O and dried over Na2SO4. After filtration, the organic phase was concentrated and the residue purified by chromatography over silica gel using CH2Cl2/MeOH/HOAc/H2O=90/10/1/1 as eluent followed by preparative HPLC (eluent: CH3CN/H2O/0.1% CF3COOH). The fractions containing the product were combined and concentrated in vacuo. The residue was lyophilized with 2 equivalents 1N HCl in a H2O/CH3CN mixture yielding the hydrochloride salt of the desired product.

Workup

  1. stirringthe mixture stirred for 3 h at room temperature
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue dissolved in CH2Cl2
  4. washthe CH2Cl2 phase washed with H2O
  5. dry with materialdried over Na2SO4
  6. filtrationAfter filtration
  7. concentrationthe organic phase was concentrated
  8. customthe residue purified by chromatography over silica gel
  9. additionThe fractions containing the product
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fa09a2c0bb344f8791fdcc06e66a38bb
Source dataset
uspto-grants-2008_01
Patent number
US07317027B2

Reaction notes

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