Triethylamine → {(S)-1-[(R)-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]ethyl}carbamic acid tert-butyl ester

HRID 729420

반응식

HRID 729420 반응식
[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:34])[NH:26][C@@H:27]([C@H:29]1[CH2:33][CH2:32][NH:31][CH2:30]1)[CH3:28])([CH3:23])([CH3:22])[CH3:21].C(N(CC)CC)C>C(#N)C>[C:20]([O:24][C:25](=[O:34])[NH:26][C@H:27]([C@@H:29]1[CH2:33][CH2:32][N:31]([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])[CH2:30]1)[CH3:28])([CH3:21])([CH3:22])[CH3:23]

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 10104699(3S,1R)-3-(1-(t-butoxycarbonylamino)ethyl)pyrrolidineHCID 219788755-Amino-8,9-difluoro-3-methyl-2,3-dihydro-1-oxa-3a,5-diazaphenalene-4,6-dione

생성물 1

HCID 58681905{(S)-1-[(R)-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]ethyl}carbamic acid tert-butyl ester수율 73.7%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

A solution of 0.11 g (0.41 mmol) of 5-amino-8,9-difluoro-3-methyl-2,3-dihydro-1-oxa-3a,5-diazaphenalene-4,6-dione (Example 24h), 0.26 g (1.3 mmol) of ((R)-(S)-1-pyrrolidin-3-ylethyl)carbamic acid tert-butyl ester (J. Het. Chem., 1992; 29:1481), 0.25 g (2.5 mmol) of triethylamine and 10 mL of acetonitrile is heated at reflux for 18 hours. The solvent is removed in vacuo and the residue is partitioned between ethyl acetate/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 0.14 g of the title compound. 1H NMR (400 MHz, CDCl3): 7.43 (d, 1H), 5.24 (bs, 2H), 4.82 (m, 1H), 4.56 (m, 1H), 4.33 (d, 1H), 3.99 (m, 1H), 3.86 (m, 1H), 3.73 (m, 1H), 3.59 (m, 2H), 2.18 (m, 1H), 3.01 (m, 1H), 1.67 (m, 1H), 1.44 (s, 9H), 1.40 (m, 3H), 1.25 (m, 1H), 1.20 (d, 3H).

후처리

  1. temperatureat reflux for 18 hours
  2. customThe solvent is removed in vacuo
  3. customthe residue is partitioned between ethyl acetate/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)

출처 및 근거

ORD 기록
ord-89d51942caa243899dfbc6946eab7893
출처 데이터셋
uspto-grants-2009_09
특허 번호
US07582627B2

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