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

HRID 924495ノート

反応式

HRID 924495 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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.)

出典と根拠

ORDレコード
ord-daddb9d236dd437cb98addffe0609be7
出典データセット
uspto-grants-2016_03
特許番号
US09278950B2

反応ノート

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