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Methyl Isocyanate → 6-[2-(3-Methyl-ureido)-pyrimidin-4-yloxy]-naphthalene-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide

HRID 1094506
ノート
印刷プレビュー

反応式

HRID 1094506 の反応式
[CH3:1][N:2]=[C:3]=[O:4].[F:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13]([C:15]2[C:24]3[C:19](=[CH:20][C:21]([O:25][C:26]4[CH:31]=[CH:30][N:29]=[C:28]([NH2:32])[N:27]=4)=[CH:22][CH:23]=3)[CH:18]=[CH:17][CH:16]=2)=[O:14])=[CH:8][C:7]=1[C:33]([F:36])([F:35])[F:34]>C1COCC1.CCOC(C)=O.O>[F:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13]([C:15]2[C:24]3[C:19](=[CH:20][C:21]([O:25][C:26]4[CH:31]=[CH:30][N:29]=[C:28]([NH:32][C:3]([NH:2][CH3:1])=[O:4])[N:27]=4)=[CH:22][CH:23]=3)[CH:18]=[CH:17][CH:16]=2)=[O:14])=[CH:8][C:7]=1[C:33]([F:34])([F:36])[F:35]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 2

HCID 12228Methyl Isocyanate2 回HCID 160715501-Naphthalenecarboxamide, 6-[(2-amino-4-pyrimidinyl)oxy]-N-[4-fluoro-3-(trifluoromethyl)phenyl]-

生成物 1

HCID 236528656-[2-(3-Methyl-ureido)-pyrimidin-4-yloxy]-naphthalene-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran
溶媒
HCID 8857Ethyl Acetate溶媒

実験手順

130 μl (2.2 mMol) methyl isocyanate are added to a solution of 300 mg (0.68 mMol) 6-(2-amino-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide (Step 10.3) in 10 ml THF in a sealed vessel. The mixture is stirred at 100° C. for 11 days (another 1.1 eq. of Me-NCO is added on day 8 and 9). Then the reaction mixture is diluted with EtOAc and water, the aq. phase separated off and extracted twice with EtOAc. The organic layers are washed with water and brine, dried (Na2SO4) and partially concentrated. Precipitation with hexane, filtration and re-crystallization from boiling THF/CH3CN gives the title compound: m.p.: 233-234° C.

後処理

  1. additionis added on day 8 and 9)
  2. customthe aq. phase separated off
  3. extractionextracted twice with EtOAc
  4. washThe organic layers are washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationpartially concentrated
  7. customPrecipitation
  8. filtrationwith hexane, filtration and re-crystallization

出典と根拠

ORDレコード
ord-89a8a37433684e149257d1681d5f4657
出典データセット
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08133886B2

反応ノート

読み込み中…

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