(3R)-1-ethylpyrrolidin-3-amine → (1aRS,7bSR)-5-{2-[2-((R)-1-ethylpyrrolidin-3-ylamino)ethyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydro-cyclopropa[c]chromene-4-carboxylic acid

HRID 927886노트

반응식

HRID 927886 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[C:21]([C:22]([OH:24])=[O:23])=[C:20]3[C:15]([CH:16]4[CH2:25][CH:17]4[CH2:18][O:19]3)=[CH:14][CH:13]=2)(=[O:10])=[O:9])=[C:4]([CH:26]=[CH2:27])[CH:3]=1.[CH2:28]([N:30]1[CH2:34][CH2:33][C@@H:32]([NH2:35])[CH2:31]1)[CH3:29]>C(O)CO.O>[CH2:28]([N:30]1[CH2:34][CH2:33][C@@H:32]([NH:35][CH2:27][CH2:26][C:4]2[CH:3]=[C:2]([F:1])[CH:7]=[CH:6][C:5]=2[S:8]([NH:11][C:12]2[C:21]([C:22]([OH:24])=[O:23])=[C:20]3[C:15]([CH:16]4[CH2:25][CH:17]4[CH2:18][O:19]3)=[CH:14][CH:13]=2)(=[O:9])=[O:10])[CH2:31]1)[CH3:29]

참가 물질

5

반응물 2

HCID 51663642(3R)-1-ethylpyrrolidin-3-amine2회HCID 86713253(1aRS,7bSR)-5-(4-fluoro-2-vinylbenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid2회

생성물 1

HCID 86713267(1aRS,7bSR)-5-{2-[2-((R)-1-ethylpyrrolidin-3-ylamino)ethyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydro-cyclopropa[c]chromene-4-carboxylic acid수율 2.6%

시약·촉매·용매 2

HCID 174Ethylene Glycol용매HCID 962Water용매

실험 절차

A solution of (1aRS,7bSR)-5-(4-fluoro-2-vinylbenzenesulfonylamino)-1,1a,2,7b-tetrahydro-cyclopropa[c]chromene-4-carboxylic acid (Intermediate 74, 0.150 g) and (R)-1-ethylpyrrolidin-3-ylamine (Intermediate 193, 0.25 g) in ethylene glycol (1 ml) was irradiated in the microwave at 200° C. for 30 minutes. After cooling, the mixture was diluted with water and loaded onto a SCX-2 SPE cartridge then washed with water, methanol and 2M ammonia in methanol. The basic fractions were combined and evaporated to dryness. The residue was purified by preparative HPLC (C18) eluting with a mixture of methanol and water, containing 0.1% ammonia, with a gradient of 10-98%. Then further purified by preparative HPLC (C18) eluting with a mixture of acetonitrile and water, containing 0.1% formic acid, with a gradient of 10-60% to give (1aRS,7bSR)-5-{2-[2-((R)-1-ethylpyrrolidin-3-ylamino)ethyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydro-cyclopropa[c]chromene-4-carboxylic acid (0.005 g) as a white solid.

후처리

  1. temperatureAfter cooling
  2. washthen washed with water, methanol and 2M ammonia in methanol
  3. customevaporated to dryness
  4. customThe residue was purified by preparative HPLC (C18)
  5. washeluting with a mixture of methanol and water
  6. additioncontaining 0.1% ammonia
  7. customThen further purified by preparative HPLC (C18)
  8. washeluting with a mixture of acetonitrile and water
  9. additioncontaining 0.1% formic acid

출처 및 근거

ORD 기록
ord-0914c29cb9e046b7aa48be0276175582
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09290472B2

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