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

HRID 874913ノート

反応式

HRID 874913 の反応式
[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

参加物

7

反応物 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 ester2 回

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
70 °C

実験手順

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]+).

後処理

  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

出典と根拠

ORDレコード
ord-c841b1aae19d4577a8a2338cabc67f85
出典データセット
uspto-grants-2015_03
特許番号
US08981087B2

反応ノート

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