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Methyl 5-amino-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate → methyl (1aRS,7bSR)-5-{4-fluoro-2-[1-(2,2,2-trifluoroacetyl)azetidin-3-yl]benzene-sulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate

HRID 927973
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HRID 927973 반응식
C[C:2]1[C:3]([CH:13]2[CH2:16][N:15]([C:17](=[O:22])[C:18]([F:21])([F:20])[F:19])[CH2:14]2)=[C:4]([S:9](Cl)(=[O:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[NH2:23][C:24]1[C:33]([C:34]([O:36][CH3:37])=[O:35])=[C:32]2[C:27]([CH:28]3[CH2:38][CH:29]3[CH2:30][O:31]2)=[CH:26][CH:25]=1>N1C=CC=CC=1.C(Cl)Cl>[F:8][C:7]1[CH:6]=[CH:5][C:4]([S:9]([NH:23][C:24]2[C:33]([C:34]([O:36][CH3:37])=[O:35])=[C:32]3[C:27]([CH:28]4[CH2:38][CH:29]4[CH2:30][O:31]3)=[CH:26][CH:25]=2)(=[O:10])=[O:11])=[C:3]([CH:13]2[CH2:14][N:15]([C:17](=[O:22])[C:18]([F:20])([F:19])[F:21])[CH2:16]2)[CH:2]=1
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참가 물질

5

반응물 2

HCID 86713293Methyl 5-amino-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2회HCID 86713313Methyl 4-fluoro-2-[1-(2,2,2-trifluoroacetyl)azetidin-3-yl]benzenesulfonyl chloride2회

생성물 1

HCID 86713312methyl (1aRS,7bSR)-5-{4-fluoro-2-[1-(2,2,2-trifluoroacetyl)azetidin-3-yl]benzene-sulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate수율 104.2%

시약·촉매·용매 2

HCID 1049
Pyridine
용매
HCID 6344Dichloromethane용매2회

실험 절차

A solution of methyl 4-fluoro-2-[1-(2,2,2-trifluoroacetyl)azetidin-3-yl]benzenesulfonyl chloride (Intermediate 89, 0.192 g) and methyl (1aRS,7bSR)-5-amino-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (Intermediate 42, 0.122 g) in pyridine (1 mL) and DCM (3 mL) was left to stand at room temperature for 18 hours. The mixture was diluted with DCM, washed with 1M hydrochloric acid and filtered through a phase separator. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-30% to give methyl (1aRS,7bSR)-5-{4-fluoro-2-[1-(2,2,2-trifluoro-acetyl)azetidin-3-yl]benzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (0.294 g) as a colourless gum.

후처리

  1. washwashed with 1M hydrochloric acid
  2. filtrationfiltered through a phase separator
  3. concentrationThe filtrate was concentrated in vacuo
  4. customthe residue was purified by chromatography on silica
  5. washeluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-30%

출처 및 근거

ORD 기록
ord-baf4c76619c741e08abc8716f3035ef0
출처 데이터셋
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09290472B2

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