Cesium carbonate → 3-{[(Benzyloxy)carbonyl]amino}-7-(3-oxomorpholin-4-yl)quinoline-2-carboxylic acid

HRID 924495Notes

Reaction equation

HRID 924495 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][O:31][CH2:30][C:29]1=[O:34].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.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:28]1[CH2:33][CH2:32][O:31][CH2:30][C:29]1=[O:34])[CH:16]=2)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 669533-MorpholinoneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86726857Ethyl 3-(((benzyloxy)carbonyl)amino)-7-bromoquinoline-2-carboxylate

Product 1

HCID 867269403-{[(Benzyloxy)carbonyl]amino}-7-(3-oxomorpholin-4-yl)quinoline-2-carboxylic acidYield 25.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of ethyl 3-{[(benzyloxy)carbonyl]amino}-7-bromoquinoline-2-carboxylate (316 mg, 0.736 mmol), morpholin-3-one (100 mg, 1 mmol), Pd(OAc)2 (20 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.041 g, 0.071 mmol), and Cs2CO3 (0.31 g, 0.95 mmol) in dioxane (1.0 mL) was purged with nitrogen and then heated at 100° C. in a sealed vial for 3 h. To the cooled mixture, 5 mL of MeOH and 2 mL of 2 M NaOH were added. The resulting mixture was heated at 80° C. for 30 min. The solution was allowed to cool and NH4Cl solution and 10 mL of MeOH were added. The resulting mixture was filtered and the filtrate was 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 (0.080 g, 20%). LCMS calc. for C22H20N3O6 [M+H]+: m/z=422.1. found: 422.2.

Workup

  1. customwas purged with nitrogen
  2. additionTo the cooled mixture, 5 mL of MeOH and 2 mL of 2 M NaOH were added
  3. temperatureThe resulting mixture was heated at 80° C. for 30 min
  4. temperatureto cool
  5. additionNH4Cl solution and 10 mL of MeOH were added
  6. filtrationThe resulting mixture was filtered
  7. customthe filtrate was purified by preparative HPLC (XBridge™ C18 column
  8. washeluting with a gradient of MeCN/water containing 0.1% NH4OH, at a flow rate of 60 mL/min.)

Sources & evidence

ORD record
ord-daddb9d236dd437cb98addffe0609be7
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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