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2-Dimethylaminopyridine → N-(4-Fluoro-2-(methylcarbamoyl)benzyl)-3-(benzyloxy)-10,10-dimethyl-4-oxo-6,7,8,10-tetrahydro-4H-pyrimido[2,1-c][1,4]oxazepine-2-carboxamide

HRID 1788177
ノート
印刷プレビュー

反応式

HRID 1788177 の反応式
[CH2:1]([O:8][C:9]1[C:19](=[O:20])[N:18]2[C:12]([C:13]([CH3:22])([CH3:21])[O:14][CH2:15][CH2:16][CH2:17]2)=[N:11][C:10]=1[C:23](O)=[O:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.FC(F)(F)C(O)=O.[NH2:57][CH2:58][C:59]1[CH:68]=[CH:67][C:66]([F:69])=[CH:65][C:60]=1[C:61]([NH:63][CH3:64])=[O:62].CN(C1C=CC=CN=1)C>CN(C)C=O>[F:69][C:66]1[CH:67]=[CH:68][C:59]([CH2:58][NH:57][C:23]([C:10]2[N:11]=[C:12]3[N:18]([C:19](=[O:20])[C:9]=2[O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:17][CH2:16][CH2:15][O:14][C:13]3([CH3:21])[CH3:22])=[O:24])=[C:60]([C:61](=[O:62])[NH:63][CH3:64])[CH:65]=1
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 4

HCID 218852-DimethylaminopyridineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210698142-(Aminomethyl)-5-fluoro-n-methylbenzamide trifluoroacetate saltHCID 210698553-(Benzyloxy)-10,10-dimethyl-4-oxo-6,7,8,10-tetrahydro-4H-pyrimido[2,1-c][1,4]oxazepine-2-carboxylic acid

生成物 1

HCID 21070020
N-(4-Fluoro-2-(methylcarbamoyl)benzyl)-3-(benzyloxy)-10,10-dimethyl-4-oxo-6,7,8,10-tetrahydro-4H-pyrimido[2,1-c][1,4]oxazepine-2-carboxamide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A solution of intermediate 35, 3-(benzyloxy)-10,10-dimethyl-4-oxo-6,7,8,10-tetrahydro-4H-pyrimido[2,1-c][1,4]oxazepine-2-carboxylic acid in anhydrous dimethylformamide (4 mL) was treated with HATU (0.278 g, 0.70 mmol) and stirred for 10 minutes. The reaction mixture was treated with 2-(aminomethyl)-5-fluoro-N-methylbenzamide trifluoroacetic acid salt (0.24 g, 0.8 mmol), followed by dimethylaminopyridine (0.121 g, 0.97 mmol), then stirred for 4 hours at 60° C. Following this, the solvent was removed in vacuo and the remaining residue dissolved in ethyl acetate (15 mL) and washed with 1.0 N HCl (15 mL). The organic layer was dried (sodium sulfate), filtered, and concentrated to dryness. The crude product was purified by flash column chromatography (SiO2), eluting with ethyl acetate. Fractions containing the product were pooled, concentrated to dryness and triturated with ether to provide 0.366 g of the title compound as a white glassy solid. 1H NMR (500 MHz, d6-acetone) δ ppm: 8.71-8.82 (1H, m), 7.84-7.95 (1H, br), 7.47-7.62 (4H, m), 7.27-7.40 (5H, m), 7.20 (1H, dt, J=8.5, 2.7 Hz), 5.15-5.21 (2H, br, s), 4.48-4.60 (4H, m), 2.96 (2H, s), 2.94 (2H, s), 1.62-1.64 (6H, s).

後処理

  1. stirringstirred for 4 hours at 60° C
  2. customwas removed in vacuo
  3. dissolutionthe remaining residue dissolved in ethyl acetate (15 mL)
  4. washwashed with 1.0 N HCl (15 mL)
  5. dry with materialThe organic layer was dried (sodium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe crude product was purified by flash column chromatography (SiO2)
  9. washeluting with ethyl acetate
  10. additionFractions containing the product
  11. concentrationconcentrated to dryness
  12. customtriturated with ether

出典と根拠

ORDレコード
ord-98ddb2dfb91f401bbb52b15010d7bf0c
出典データセット
uspto-grants-2009_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07511037B2

反応ノート

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このページの内容参加物実験手順後処理出典と根拠反応ノート