Triethylamine → [(S)-1-(5-Amino-8-fluoro-3-methyl-4,6-dioxo-2,3,5,6-tetrahydro-4H-1-oxa-3a, 5-diazaphenalen-9-yl)pyrrolidin-3-yl]carbamic acid tert-butyl ester

HRID 729419

反応式

HRID 729419 の反応式
[NH2:1][N:2]1[C:13](=[O:14])[C:12]2[C:15]3[N:4]([CH:5]([CH3:18])[CH2:6][O:7][C:8]=3[C:9](F)=[C:10]([F:16])[CH:11]=2)[C:3]1=[O:19].[C:20]([O:24][C:25](=[O:32])[NH:26][C@H:27]1[CH2:31][CH2:30][NH:29][CH2:28]1)([CH3:23])([CH3:22])[CH3:21].C(N(CC)CC)C>C(#N)C>[C:20]([O:24][C:25](=[O:32])[NH:26][C@H:27]1[CH2:31][CH2:30][N:29]([C:9]2[C:8]3=[C:15]4[C:12]([C:13](=[O:14])[N:2]([NH2:1])[C:3](=[O:19])[N:4]4[CH:5]([CH3:18])[CH2:6][O:7]3)=[CH:11][C:10]=2[F:16])[CH2:28]1)([CH3:23])([CH3:21])[CH3:22]

参加物

5

反応物 3

HCID 8471TriethylamineHCID 1514396(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 219788755-Amino-8,9-difluoro-3-methyl-2,3-dihydro-1-oxa-3a,5-diazaphenalene-4,6-dione

生成物 1

HCID 69073124[(S)-1-(5-Amino-8-fluoro-3-methyl-4,6-dioxo-2,3,5,6-tetrahydro-4H-1-oxa-3a, 5-diazaphenalen-9-yl)pyrrolidin-3-yl]carbamic acid tert-butyl ester収率 104.1%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

A solution of 0.2 g (0.75 mmol) of 5-amino-8,9-difluoro-3-methyl-2,3-dihydro-1-oxa-3a,5-diazaphenalene-4,6-dione (Example 24h), 0.58 g (2.0 mmol) of (S)-3-pyrrolidinylcarbamic acid tert-butyl ester (J. Med. Chem., 1992; 35:1764), 0.5 g (0.5 mmol) of triethylamine and 20 mL of acetonitrile is heated at reflux for 18 hours. The solvent is removed in vacuo and the residue is partitioned between dichloromethane-water. The organic layer is washed with water, dried (MgSO4) and concentrated in vacuo. The residue is chromatographed over flash grade silica gel (230-400 mesh) eluting with dichloromethane/ethanol (95:5) to give 0.34 g of the title compound, mp 114-116° C.

後処理

  1. temperatureat reflux for 18 hours
  2. customThe solvent is removed in vacuo
  3. customthe residue is partitioned between dichloromethane-water
  4. washThe organic layer is washed with water
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue is chromatographed over flash grade silica gel (230-400 mesh)
  8. washeluting with dichloromethane/ethanol (95:5)

出典と根拠

ORDレコード
ord-d527ea1096be499f84021be0537536a4
出典データセット
uspto-grants-2009_09
特許番号
US07582627B2

関連ノート

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