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 928051노트

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HRID 928051 반응식
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]

참가 물질

7

반응물 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 acid2회HCID 86713343methyl (1aRS,7bSR)-5-(2-aminomethyl-4-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2회

생성물 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-carboxylate수율 58.1%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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%

출처 및 근거

ORD 기록
ord-0cb5ffb0d23d4ef0999889cf55ac6c3a
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09290472B2

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