Diisopropylethylamine → methyl (1aRS,7bSR)-5-{2-[((S)-1-ethylpyrrolidin-2-yl)cabonyl-aminomethyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate

HRID 927984ノート

反応式

HRID 927984 の反応式
[NH2:1][CH2:2][C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[S:10]([NH:13][C:14]1[C:23]([C:24]([O:26][CH3:27])=[O:25])=[C:22]2[C:17]([CH:18]3[CH2:28][CH:19]3[CH2:20][O:21]2)=[CH:16][CH:15]=1)(=[O:12])=[O:11].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:53]([N:55]1[CH2:59][CH2:58][CH2:57][C@H:56]1[C:60](O)=[O:61])[CH3:54].C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH2:53]([N:55]1[CH2:59][CH2:58][CH2:57][C@H:56]1[C:60]([CH:2]([NH2:1])[C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[S:10]([NH:13][C:14]1[C:23]([C:24]([O:26][CH3:27])=[O:25])=[C:22]2[C:17]([CH:18]3[CH2:28][CH:19]3[CH2:20][O:21]2)=[CH:16][CH:15]=1)(=[O:11])=[O:12])=[O:61])[CH3:54]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 283547181-ethyl-L-Proline2 回HCID 86713343methyl (1aRS,7bSR)-5-(2-aminomethyl-4-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2 回

生成物 1

HCID 131735054methyl (1aRS,7bSR)-5-{2-[((S)-1-ethylpyrrolidin-2-yl)cabonyl-aminomethyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate収率 75%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A mixture of methyl (1aRS,7bSR)-5-(2-aminomethyl-4-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 102, 0.515 g), HATU (0.483 g), (S)—N-ethylpyrrolidine-2-carboxylic acid (Intermediate 106, 0.182 g) and N,N-di-isopropyl-N-ethylamine (0.328 g) in dry DMF (25 mL) was stirred at room temperature for 2 hours. The mixture was concentrated under vacuum and the residue was diluted with water and extracted with ethyl acetate, washed with water, dried (MgSO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM, with a gradient of 1-2% to give methyl (1aRS,7bSR)-5-{2-[((S)-1-ethylpyrrolidin-2-yl)cabonyl-aminomethyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (0.505 g) as a glassy solid.

後処理

  1. concentrationThe mixture was concentrated under vacuum
  2. additionthe residue was diluted with water
  3. extractionextracted with ethyl acetate
  4. washwashed with water
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customThe filtrate was evaporated to dryness
  8. customthe residue was purified by chromatography on silica
  9. washeluting with a mixture of methanol and DCM, with a gradient of 1-2%

出典と根拠

ORDレコード
ord-d0a7ed7ded52495ba385cf75281a10cd
出典データセット
uspto-grants-2016_03
特許番号
US09290472B2

反応ノート

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