4-Methylmorpholine → Methyl (1aRS,7bSR)-5-(2-{[((S)-1-ethylpyrrolidine-3-carbonyl)amino]methyl}-4-fluoro-benzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate

HRID 928051ノート

反応式

HRID 928051 の反応式
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:25]([N:27]1[CH2:31][CH2:30][C@H:29]([C:32]([OH:34])=O)[CH2:28]1)[CH3:26].CN1CCOCC1.[NH2:42][CH2:43][C:44]1[CH:49]=[C:48]([F:50])[CH:47]=[CH:46][C:45]=1[S:51]([NH:54][C:55]1[C:64]([C:65]([O:67][CH3:68])=[O:66])=[C:63]2[C:58]([CH:59]3[CH2:69][CH:60]3[CH2:61][O:62]2)=[CH:57][CH:56]=1)(=[O:53])=[O:52]>CN(C=O)C.O>[CH2:25]([N:27]1[CH2:31][CH2:30][C@H:29]([C:32]([NH:42][CH2:43][C:44]2[CH:49]=[C:48]([F:50])[CH:47]=[CH:46][C:45]=2[S:51]([NH:54][C:55]2[C:64]([C:65]([O:67][CH3:68])=[O:66])=[C:63]3[C:58]([CH:59]4[CH2:69][CH:60]4[CH2:61][O:62]3)=[CH:57][CH:56]=2)(=[O:52])=[O:53])=[O:34])[CH2:28]1)[CH3:26]

参加物

7

反応物 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 28064096(S)-1-ethylpyrrolidine-3-carboxylic acid2 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 71006923Methyl (1aRS,7bSR)-5-(2-{[((S)-1-ethylpyrrolidine-3-carbonyl)amino]methyl}-4-fluoro-benzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate収率 58.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

HATU (0.234 g) was added to a mixture of (S)-1-ethylpyrrolidine-3-carboxylic acid (Intermediate 189, 0.089 g) and NMM (0.068 mL) in DMF (4 mL) and the mixture was stirred for 15 minutes. Methyl (1aRS,7bSR)-5-(2-aminomethyl-4-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 102, 0.250 g) was added and the mixture was stirred for 20 hours. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated NaHCO3 solution, dried (Na2SO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica eluting with a mixture of 2M ammonia in methanol and DCM with a gradient of 0-15% to give methyl (1aRS,7bSR)-5-(2-{[((S)-1-ethylpyrrolidine-3-carbonyl)amino]methyl}-4-fluoro-benzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (0.190 g) as a solid.

後処理

  1. stirringthe mixture was stirred for 20 hours
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated NaHCO3 solution
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customThe filtrate was evaporated to dryness
  7. customthe residue was purified by chromatography on silica eluting with a mixture of 2M ammonia in methanol and DCM with a gradient of 0-15%

出典と根拠

ORDレコード
ord-0cb5ffb0d23d4ef0999889cf55ac6c3a
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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