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

HRID 924495노트

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HRID 924495 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

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.

후처리

  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.)

출처 및 근거

ORD 기록
ord-daddb9d236dd437cb98addffe0609be7
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09278950B2

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