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

HRID 476390ノート

反応式

HRID 476390 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.[F:33][C:34]([CH3:39])([CH3:38])[C:35](O)=[O:36].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[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:35](=[O:36])[C:34]([F:33])([CH3:39])[CH3:38])[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 4

HCID 81531DiisopropylethylamineHCID 27828282-Fluoro-2-methylpropanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59596940N-(4-((2-aminopyridin-4-yl)oxy)-2,5-difluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

生成物 1

HCID 54576514N-(2,5-difluoro-4-((2-(2-fluoro-2-methylpropanamido)pyridin-4-yl)oxy)phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide収率 43%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane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 (250 mg, 0.565 mmol) and 2-fluoro-2-methylpropanoic acid (108 mg, 1.02 mmol) in anhydrous CH2Cl2 (30 mL) was added HATU (323 mg, 0.85 mmol) and DIPEA (2.5 mL) under N2. This reaction mixture was stirred at room temperature overnight. The solvent was removed in vacuo. The residue was poured into water (100 mL), extracted with ethyl acetate (3×50 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. This crude product was purified by silica gel chromatography to give N-(2,5-difluoro-4-((2-(2-fluoro-2-methylpropanamido)pyridin-4-yl)oxy)phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (128 mg, 43% yield). 1H-NMR (400 MHz, Methanol-d4): δ 8.21-8.17 (m, 2H), 7.73 (d, J=2.4 Hz, 1H), 7.54-7.51 (m, 2H), 7.23 (dd, J=10.8, 7.2 Hz, 1H), 7.08-7.04 (m, 2H), 6.75 (dd, J=5.6, 2.4 Hz, 1H), 1.76-1.69 (m, 4H), 1.62 (s, 3H), 1.56 (s, 3H); MS (ESI): m/z 531.1 [M+H]+.

後処理

  1. customThe solvent was removed in vacuo
  2. additionThe residue was poured into water (100 mL)
  3. extractionextracted with ethyl acetate (3×50 mL)
  4. washwashed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThis crude product was purified by silica gel chromatography

出典と根拠

ORDレコード
ord-b94d8eeecccd4407bbad760821e19c91
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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