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

HRID 924488Notes

Reaction equation

HRID 924488 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.[NH:28]1[CH2:33][CH2:32][NH:31][CH2:30][C:29]1=[O:34].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:31]1[CH2:32][CH2:33][NH:28][C:29](=[O:34])[CH2:30]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 231360Piperazin-2-oneHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 86726857Ethyl 3-(((benzyloxy)carbonyl)amino)-7-bromoquinoline-2-carboxylate

Product 1

HCID 867269333-{[(Benzyloxy)carbonyl]amino}-7-(3-oxopiperazin-1-yl)quinoline-2-carboxylic acidYield 7%

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), piperazin-2-one (120 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 deoxygenated and purged with nitrogen then heated at 100° C. in a sealed vial for 3 h. To the mixture resulting mixture, 20 mL of EtOAc and 20 mL of water were added. The precipitates collected by filtration and purified by preparative HPLC (XBridge™ C18 column, eluting with a gradient of MeCN/water containing 0.1% NH4OH, at a flow rate of 60 mL/min.) to afford the sub-title compound (0.017 g, 6.9%). LCMS calc. for C22H21N4O5 [M+H]+: m/z=421.1. found: 421.2.

Workup

  1. customwas deoxygenated
  2. custompurged with nitrogen
  3. customTo the mixture resulting mixture, 20 mL of EtOAc and 20 mL of water
  4. additionwere added
  5. filtrationThe precipitates collected by filtration
  6. custompurified by preparative HPLC (XBridge™ C18 column
  7. washeluting with a gradient of MeCN/water containing 0.1% NH4OH, at a flow rate of 60 mL/min.)

Sources & evidence

ORD record
ord-6224b23484c44d41bfe765af2228da91
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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