Triethylamine → N-(4-(3-Bromopyridin-4-yloxy)-2,5-difluorophenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

HRID 1046026ノート

反応式

HRID 1046026 の反応式
[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:14]([F:15])=[CH:13][C:12]([NH2:16])=[C:11]([F:17])[CH:10]=1.C(N(CC)CC)C.[F:25][C:26]1[CH:31]=[CH:30][C:29]([N:32]2[CH:37]=[CH:36][CH:35]=[C:34]([C:38](Cl)=[O:39])[C:33]2=[O:41])=[CH:28][CH:27]=1>C1COCC1>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:14]([F:15])=[CH:13][C:12]([NH:16][C:38]([C:34]2[C:33](=[O:41])[N:32]([C:29]3[CH:28]=[CH:27][C:26]([F:25])=[CH:31][CH:30]=3)[CH:37]=[CH:36][CH:35]=2)=[O:39])=[C:11]([F:17])[CH:10]=1

参加物

5

反応物 3

HCID 8471TriethylamineHCID 596809561-(4-Fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carbonyl chlorideHCID 673992554-(3-Bromopyridin-4-yloxy)-2,5-difluorobenzenamine

生成物 1

HCID 68009215N-(4-(3-Bromopyridin-4-yloxy)-2,5-difluorophenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide収率 71.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A solution of Example A2 (0.100 g, 0.332 mmol) in THF (1 mL) was treated with triethylamine (0.069 ml, 0.498 mmol) and a suspension of 1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carbonyl chloride (0.125 g, 0.498 mmol) in THF (2 mL). The mixture was blanketed with argon and stirred overnight at room temperature. The solids were removed via filtration, rinsed with THF and the filtrate was concentrated to dryness. The crude material was purified by silica gel chromatography (10-100% EtOAc/Hex) to afford N-(4-(3-bromopyridin-4-yloxy)-2,5-difluorophenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (122 mg, 71% yield) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 12.45 (s, 1H); 8.74 (s, 1H); 8.58 (m, 2H); 8.38 (d, J=5.6 Hz, 1H); 8.15 (dd, J=6.6, 2.2 Hz, 1H); 7.67 (dd, J=11.0, 7.3 Hz, 1H); 7.60 (dd, J=8.8, 4.9 Hz, 2H); 7.41 (t, J=8.7 Hz, 2H); 6.89 (d, J=5.6 Hz, 1H); 6.74 (t, J=7.0 Hz, 1H); MS (ESI) m/z: 516.0, 518.0 (M+H+).

後処理

  1. customThe solids were removed via filtration
  2. washrinsed with THF
  3. concentrationthe filtrate was concentrated to dryness
  4. customThe crude material was purified by silica gel chromatography (10-100% EtOAc/Hex)

出典と根拠

ORDレコード
ord-d5610eb7ca5f4b17b83fcd4f76568bd3
出典データセット
uspto-grants-2013_10
特許番号
US08569319B2

反応ノート

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