Potassium Phosphate, Tribasic → 3-{[(Benzyloxy)carbonyl]amino}-7-(4-methyl-3-oxopiperazin-1-yl)quinoline-2-carboxylic acid

HRID 924485Notes

Reaction equation

HRID 924485 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13]([C:23]([O:25]CC)=[O:24])=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[C:17](Br)[CH:16]=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:28][N:29]1[CH2:34][CH2:33][NH:32][CH2:31][C:30]1=[O:35].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(O)(C)(C)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13]([C:23]([OH:25])=[O:24])=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[C:17]([N:32]1[CH2:33][CH2:34][N:29]([CH3:28])[C:30](=[O:35])[CH2:31]1)[CH:16]=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 43990421-Methylpiperazin-2-oneHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 86726857Ethyl 3-(((benzyloxy)carbonyl)amino)-7-bromoquinoline-2-carboxylate

Product 1

HCID 867269303-{[(Benzyloxy)carbonyl]amino}-7-(4-methyl-3-oxopiperazin-1-yl)quinoline-2-carboxylic acidYield 9.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6386tert-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of ethyl 3-{[(benzyloxy)carbonyl]amino}-7-bromoquinoline-2-carboxylate (250 mg, 0.58 mmol), 1-methylpiperazin-2-one (130 mg, 1.2 mmol), Pd(OAc)2 (20 mg), dicyclohexyl(2′,6′-diisopropoxybiphenyl-2-yl)phosphine (41 mg, 0.087 mmol), and K3PO4 (490 mg, 2.3 mmol) in tert-butyl alcohol (8 mL) was purged with nitrogen then heated at 100° C. in a sealed vial for 3 h. The mixture was then allowed to cool and EtOAc and water were added. The resulting layers were separated and organic layer was concentrated under reduced pressure. To the resulting bright-yellow solid, 2 mL of dioxane, 2 mL of 2 M NaOH were added. The mixture was heated in 80° C. oil bath with stirring for 0.5 h, then allowed to cooled and neutralized with 4 mL of with 1 M HCl. The red solid formed was collected by filtration and air-dried overnight to give the sub-title compound (24 mg, 9.5%). LCMS calc. for C26H33N8O2 [M+H]+: m/z=489.3. found: 435.2.

Workup

  1. customwas purged with nitrogen
  2. temperatureto cool
  3. additionEtOAc and water were added
  4. customThe resulting layers were separated
  5. concentrationorganic layer was concentrated under reduced pressure
  6. additionTo the resulting bright-yellow solid, 2 mL of dioxane, 2 mL of 2 M NaOH were added
  7. temperatureThe mixture was heated in 80° C. oil bath
  8. temperatureto cooled
  9. customThe red solid formed
  10. filtrationwas collected by filtration
  11. customair-dried overnight

Sources & evidence

ORD record
ord-7bfa183977c545eda4a7f7e17ae8994f
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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