Triethylamine → 8-(4-Amino-2-fluoro-phenyl)-2-morpholin-4-yl-benzo[e][1,3]oxazin-4-one

HRID 874913노트

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HRID 874913 반응식
[N:1]1([C:7]2[O:8][C:9]3[C:17](OS(C(F)(F)F)(=O)=O)=[CH:16][CH:15]=[CH:14][C:10]=3[C:11](=[O:13])[N:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[F:26][C:27]1[CH:28]=[C:29]([NH2:42])[CH:30]=[CH:31][C:32]=1B1OC(C)(C)C(C)(C)O1.CCN(CC)CC>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:42][C:29]1[CH:30]=[CH:31][C:32]([C:17]2[C:9]3[O:8][C:7]([N:1]4[CH2:2][CH2:3][O:4][CH2:5][CH2:6]4)=[N:12][C:11](=[O:13])[C:10]=3[CH:14]=[CH:15][CH:16]=2)=[C:27]([F:26])[CH:28]=1

참가 물질

7

반응물 3

HCID 8471TriethylamineHCID 447552073-Fluoro-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 86665644Trifluoro-methanesulfonic acid 2-morpholin-4yl-4-oxo-4H-benzo[e][1,3]oxazin-8-yl ester2회

생성물 1

HCID 498552378-(4-Amino-2-fluoro-phenyl)-2-morpholin-4-yl-benzo[e][1,3]oxazin-4-one

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
70 °C

실험 절차

To a mixture of trifluoro-methanesulfonic acid 2-morpholin-4-yl-4-oxo-4H-benzo[e][1,3]oxazin-8-yl ester, 3 (60 mg, 0.16 mmol, 1 eq), 3-fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamine (47 mg, 0.20 mmol, 1.3 eq), Pd(PPh3)4 (7.6 mg, 0.007 mmol, 5 mol %) in dioxane (2 mL) and H2O (1mL) was added Et3N (66 mL, 0.48 mmol, 3 eq) dropwise. The reaction mixture was heated up in a pressure tube at 70° C. for 6 h. Upon cooling, the solution was partitioned between EtOAc (15 mL) and H2O (10 mL). The aqueous layer was further extracted with EtOAc (2×5 mL) and DCM (5 mL). The combined organic extracts were dried over MgSO4 and the solvent was removed in vacuuo. The residue was further purified by silica gel column chromatography with EtOAc:MeOH (1:0-13:1) to yield the product, B, as a pale brown solid (47 mg, 87%). 1HNMR (400 MHz, CDCl3+10% MeOD) δH: 7.98 (dd, J=7.5, 1.5 Hz, 1H), 7.62 (dd, 1.5 Hz, 1H), 7.42 (t, J=7.5 Hz, 1H), 7.12 (t, J=8.3 Hz, 1H), 6.59 (dd, J=8.3, 2.3 Hz, 1H), 6.52 (dd, J=12.5, 2.0 Hz, 1H), 3.49-3.90 (m, 10H). MS (ES+) 342.1 (100%, [M+H]+).

후처리

  1. temperatureUpon cooling
  2. customthe solution was partitioned between EtOAc (15 mL) and H2O (10 mL)
  3. extractionThe aqueous layer was further extracted with EtOAc (2×5 mL) and DCM (5 mL)
  4. dry with materialThe combined organic extracts were dried over MgSO4
  5. customthe solvent was removed in vacuuo
  6. customThe residue was further purified by silica gel column chromatography with EtOAc:MeOH (1:0-13:1)
  7. customto yield the product, B

출처 및 근거

ORD 기록
ord-c841b1aae19d4577a8a2338cabc67f85
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08981087B2

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