Cyanoacetic acid → N-(4-(2-(2-cyanoacetamido)pyridin-4-yloxy)-2,5-difluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 476380ノート

反応式

HRID 476380 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:33]([CH2:35][C:36](O)=[O:37])#[N:34].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>CN(C=O)C.C(OCC)(=O)C.O>[C:33]([CH2:35][C:36]([NH: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:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=4)=[O:23])[CH2:21][CH2:20]3)=[O:18])=[C:11]([F:32])[CH:10]=2)[CH:5]=[CH:4][N:3]=1)=[O:37])#[N:34]

参加物

8

反応物 4

HCID 9740Cyanoacetic acidHCID 81531DiisopropylethylamineHCID 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 54576510N-(4-(2-(2-cyanoacetamido)pyridin-4-yloxy)-2,5-difluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide収率 64.5%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

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 (150 mg, 0.34 mmol) (as prepared in Example 9) and 2-cyanoacetic acid (44 mg, 0.51 mmol) in DMF (2 mL) was added HATU (258 mg, 0.68 mmol) and DIEA (130 mg, 1 mmol) and the mixture was stirred at 60° C. under nitrogen overnight. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (50 mL) and H2O (50 mL) and the organic layer was washed with brine, dried and concentrated under reduced pressure. The residue was purified by prep-TLC to give N-(4-(2-(2-cyanoacetamido)pyridin-4-yloxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (70 mg, yield 64.5%). 1H-NMR (400 MHz, DMSO-d6): δ 10.99 (s, 1H), 10.94 (s, 1H), 9.81 (s, 1H), 8.23 (d, J=5.6 Hz, 1H), 8.08 (dd, J=12.4, 6.8 Hz, 1H), 7.59-7.55 (m, 4H), 7.15 (t, J=8.8 Hz, 2H), 6.80 (dd, J=6.0, 2.4 Hz, 1H), 3.92 (s, 2H), 1.61-1.56 (m, 4H); MS (ESI): m/z 510.2 [M+H]+.

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washthe organic layer was washed with brine
  3. customdried
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by prep-TLC

出典と根拠

ORDレコード
ord-47b49cb258f147f2b7332d31306bc138
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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