(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 927886ノート

反応式

HRID 927886 の反応式
[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]

参加物

5

反応物 2

HCID 51663642(3R)-1-ethylpyrrolidin-3-amine2 回HCID 86713253(1aRS,7bSR)-5-(4-fluoro-2-vinylbenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid2 回

生成物 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 acid収率 2.6%

試薬・触媒・溶媒 2

HCID 174Ethylene Glycol溶媒HCID 962Water溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-0914c29cb9e046b7aa48be0276175582
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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