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 10333ノート

反応式

HRID 10333 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-e85e2ebb798446ffac97f400cdc25983
出典データセット
uspto-grants-2006_08
特許番号
US07094780B1

反応ノート

読み込み中…