Sodium Bicarbonate → 4-(4-{[(3,4-Dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)quinoline-2-carboxylic acid

HRID 2234000Notes

Reaction equation

HRID 2234000 reaction equation
[Cl:1][C:2]1[C:6]([Cl:7])=[C:5]([CH3:8])[NH:4][C:3]=1[C:9]([NH:11][CH:12]1[CH2:17][CH2:16][N:15]([C:18](OC(C)(C)C)=O)[CH2:14][CH2:13]1)=[O:10].BrC1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[N:29]=[C:28]([C:36]([OH:38])=[O:37])[CH:27]=1.C(=O)(O)[O-].[Na+]>Cl.O1CCOCC1.CN(C=O)C.O>[Cl:1][C:2]1[C:6]([Cl:7])=[C:5]([CH3:8])[NH:4][C:3]=1[C:9]([NH:11][CH:12]1[CH2:13][CH2:14][N:15]([C:18]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[N:29]=[C:28]([C:36]([OH:38])=[O:37])[CH:27]=2)[CH2:16][CH2:17]1)=[O:10]

Participants

8

Reactant 3

HCID 516892Sodium BicarbonateHCID 155308124-Bromoquinoline-2-carboxylic acidHCID 68579743tert-Butyl 4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidine-1-carboxylate2×

Product 1

HCID 114650134-(4-{[(3,4-Dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidin-1-yl)quinoline-2-carboxylic acidYield 19.3%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolvent2×HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

tert-Butyl 4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidine-1-carboxylate (Intermediate 2) (280 mg, 0.74 mmol) was suspended in 5 ml of 4.0 M HCl in dioxane and stirred for 2 h, then evaporated in vacuo to give a brown solid, which was dissolved in 20 ml of DMF. 4-Bromoquinoline-2-carboxylic acid (188 mg, 0.74 mmol) (prepared via the procedure of Y Kato, et. al., Tetrahedron Lett 2001, 42:4849-51), and sodium bicarbonate (554 mg, 6.6 mmol) were added and the resulting solution was heated under a nitrogen atmosphere with stirring for 20 h. Upon cooling to ambient temperature, the reaction was diluted with 25 ml of water, adjusted to pH 4 using concentrated HCl, filtered and the filtrate extracted with chloroform (2×25 ml). The combined organic extract was dried over sodium sulfate and concentrated in vacuo to a yellow solid, which was suspended in 10 ml of MeOH and collected by suction filtration, to afford the title compound as a yellow solid (64 mg).

Workup

  1. customevaporated in vacuo
  2. customto give a brown solid, which
  3. additionwere added
  4. temperaturethe resulting solution was heated under a nitrogen atmosphere
  5. stirringwith stirring for 20 h
  6. filtrationfiltered
  7. extractionthe filtrate extracted with chloroform (2×25 ml)
  8. extractionThe combined organic extract
  9. dry with materialwas dried over sodium sulfate
  10. concentrationconcentrated in vacuo to a yellow solid, which
  11. filtrationcollected by suction filtration

Sources & evidence

ORD record
ord-bf2cf2a0881b45d2ba3dbc4c453bc938
Source dataset
uspto-grants-2010_05
Patent number
US07709503B2

Reaction notes

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