Water → 1-(5-Tert-butylisoxazol-3-yl)-3-(5-(6,7-dimethoxyquinazolin-4-yloxy)-2,4-difluorophenyl)urea

HRID 631598

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HRID 631598 반응식
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[O:15][C:16]1[C:17]([F:24])=[CH:18][C:19]([F:23])=[C:20]([CH:22]=1)[NH2:21].CCN(C(C)C)C(C)C.[C:34]([C:38]1[O:42][N:41]=[C:40]([NH:43][C:44](=O)[O:45]C2C=CC=CC=2)[CH:39]=1)([CH3:37])([CH3:36])[CH3:35].O>C1COCC1.CN(C1C=CN=CC=1)C>[C:34]([C:38]1[O:42][N:41]=[C:40]([NH:43][C:44]([NH:21][C:20]2[CH:22]=[C:16]([O:15][C:6]3[C:5]4[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=4)[N:9]=[CH:8][N:7]=3)[C:17]([F:24])=[CH:18][C:19]=2[F:23])=[O:45])[CH:39]=1)([CH3:37])([CH3:35])[CH3:36]

참가 물질

7

반응물 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 13489605Phenyl 5-tert-butylisoxazol-3-ylcarbamateHCID 668767545-(6,7-Dimethoxyquinazolin-4-yloxy)-2,4-difluoroaniline

생성물 1

HCID 566652481-(5-Tert-butylisoxazol-3-yl)-3-(5-(6,7-dimethoxyquinazolin-4-yloxy)-2,4-difluorophenyl)urea수율 25.1%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 8028Tetrahydrofuran용매

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온도
70 °C

실험 절차

To a solution of 5-(6,7-dimethoxyquinazolin-4-yloxy)-2,4-difluoroaniline (100 mg, 0.3 mmol) in THF (10 mL), DIEA (58 mg, 0.45 mmol), DMAP (20 mg, 0.16 mmol), and phenyl 5-tert-butylisoxazol-3-ylcarbamate (117 mg, 0.32 mmol) were added and the mixture heated overnight at 70° C. The mixture was poured into water and extracted with EtOAc three times. The extracts were dried over magnesium sulfate, filtered, and concentrated. The residue was purified using silica gel chromatography eluting with EtOAc/Hexane (3-80%). The appropriate fractions were concentrated to afford 1-(5-tert-butylisoxazol-3-yl)-3-(5-(6,7-dimethoxyquinazolin-4-yloxy)-2,4-difluorophenyl)urea (37.56 mg, 25% yield). 1H NMR (300 MHz, CDCl3) δ 1.35 (s, 9H), 4.05 (s, 6H), 6.09 (s, 1H), 6.85 (s, 1H), 7.28 (s, 1H), 7.35 (s, 1H), 8.28 (m, 1H), 8.70 (s, 1H), 9.50 (s, 1H). LC-MS (ESI) m/z 500 (M+H)+

후처리

  1. extractionextracted with EtOAc three times
  2. dry with materialThe extracts were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified
  6. washeluting with EtOAc/Hexane (3-80%)
  7. concentrationThe appropriate fractions were concentrated

출처 및 근거

ORD 기록
ord-236afe88de4a453f8b0ac5bbded6c4f1
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09320739B2

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