Diisopropylethylamine → N-(2,5-difluoro-4-((2-(2-methoxyacetamido)pyridin-4-yl)oxy)phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 476379ノート

反応式

HRID 476379 の反応式
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:14]([F:15])=[CH:13][C:12]([NH:16][C:17]([C:19]3([C:22]([NH:24][C:25]4[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=4)=[O:23])[CH2:21][CH2:20]3)=[O:18])=[C:11]([F:32])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.C(N(C(C)C)CC)(C)C.[CH3:42][O:43][CH2:44][C:45](Cl)=[O:46]>C1COCC1.C(OCC)(=O)C>[F:32][C:11]1[CH:10]=[C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:45](=[O:46])[CH2:44][O:43][CH3:42])[CH:7]=2)[C:14]([F:15])=[CH:13][C:12]=1[NH:16][C:17]([C:19]1([C:22]([NH:24][C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)=[O:23])[CH2:21][CH2:20]1)=[O:18]

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 96623Methoxyacetyl chlorideHCID 59596940N-(4-((2-aminopyridin-4-yl)oxy)-2,5-difluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

生成物 1

HCID 54576301N-(2,5-difluoro-4-((2-(2-methoxyacetamido)pyridin-4-yl)oxy)phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide収率 50.3%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of N-(4-((2-aminopyridin-4-yl)oxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (130 mg, 0.29 mmol) in 10 mL, of anhydrous tetrahydrofuran was added diisopropylethylamine (75 mg, 0.58 mmol). A solution of methoxyacetyl chloride (34.5 mg, 0.32 mmol) in THF (1 mL) was added drop wise at 0° C. The resultant reaction mixture was stirred at R.T. for 0.5 h. It was diluted with ethyl acetate, washed with brine, dried over sodium sulfate and concentrated. The residue was purified by prep-TLC to give N-(2,5-difluoro-4-((2-(2-methoxyacetamido)pyridin-4-yl)oxy)phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (75 mg, 50% yield). 1H NMR (400 MHz, CDCl3): δ 9.79 (s, 1H), 8.89 (s, 1H), 8.53 (s, 1H), 8.30 (dd, J=12.0, 7.2 Hz, 1H), 8.17 (d, J=5.6 Hz, 1H), 7.83 (d, J=2.4 Hz, 1H), 7.49-7.45 (m, 2H), 7.07-6.99 (m, 3H), 6.64 (dd, J=5.6, 2.4 Hz 1H), 3.98 (s, 2H), 3.49 (s, 3H), 1.78-1.66 (m, 4H); MS (ESI): m/z 515.2 [M+H]+.

後処理

  1. customThe resultant reaction mixture
  2. washwashed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by prep-TLC

出典と根拠

ORDレコード
ord-849cbaca24aa42e4b6d319c0fab028ec
出典データセット
uspto-grants-2014_01
特許番号
US08637672B2

反応ノート

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