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Potassium Iodide → (R)-1-(5-tert-butylisoxazol-3-yl)-3-(3-(6-methoxy-7-(oxiran-2-ylmethoxy)quinazolin-4-yloxy)phenyl)urea

HRID 1917805
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HRID 1917805 반응식
[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]3[C:30]4[C:25](=[CH:26][C:27]([OH:33])=[C:28]([O:31][CH3:32])[CH:29]=4)[N:24]=[CH:23][N:22]=3)[CH:15]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:34]([C@@H:36]1[O:38][CH2:37]1)Cl.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[K+]>CN(C)C=O>[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]3[C:30]4[C:25](=[CH:26][C:27]([O:33][CH2:34][C@H:36]5[CH2:37][O:38]5)=[C:28]([O:31][CH3:32])[CH:29]=4)[N:24]=[CH:23][N:22]=3)[CH:15]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]
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참가 물질

6

반응물 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 2734062(-)-EpichlorohydrinHCID 1360737521-(5-Tert-butylisoxazol-3-yl)-3-(3-(7-hydroxy-6-methoxyquinazolin-4-yloxy)phenyl)urea

생성물 1

HCID 86653512(R)-1-(5-tert-butylisoxazol-3-yl)-3-(3-(6-methoxy-7-(oxiran-2-ylmethoxy)quinazolin-4-yloxy)phenyl)urea수율 15%

시약·촉매·용매

1
HCID 6228Dimethylformamide용매

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온도
80 °C

실험 절차

A stirred mixture of 1-(5-tert-butylisoxazol-3-yl)-3-(3-(7-hydroxy-6-methoxyquinazolin-4-yloxy)phenyl)urea from Example 95B (160 mg, 0.356 mmol), (R)-(−)-epichlorohydrin (65 mg, 0.702 mmol), cesium carbonate (120 mg, 0.356 mmol) and potassium iodide (40 mg, 0.241 mmol) in dry N,N-dimethylformamide (4 mL) was heated in a sealed vial at 80° C. in a Biotage microwave synthesizer for 90 mins. After cooling to room temperature, the mixture was partitioned between water (50 mL) and a mixture of ethyl acetate (40 mL) and tetrahydrofuran (10 mL). The organic layer was separated, washed with brine (50 mL), dried over MgSO4 and concentrated under reduced pressure. Purification via silica gel chromatography eluting with 100% dichloromethane to 5% methanol in dichloromethane to afford (R)-1-(5-tert-butylisoxazol-3-yl)-3-(3-(6-methoxy-7-(oxiran-2-ylmethoxy)quinazolin-4-yloxy)phenyl)urea as a colorless solid (27 mg, 15%). LC-MS (ESI) m/z 506 (M+H)+.

후처리

  1. temperatureAfter cooling to room temperature
  2. customthe mixture was partitioned between water (50 mL)
  3. additiona mixture of ethyl acetate (40 mL) and tetrahydrofuran (10 mL)
  4. customThe organic layer was separated
  5. washwashed with brine (50 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customPurification via silica gel chromatography
  9. washeluting with 100% dichloromethane to 5% methanol in dichloromethane

출처 및 근거

ORD 기록
ord-788770a4c46a41a2a1277239cbfe8292
출처 데이터셋
uspto-grants-2013_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08618289B2

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