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Phosgene → N-[N2-[[3-oxo-2-[(1-oxoheptyl)amino]-1-methyl-3-(phenylmethoxy)-propoxy]carbonyl]-N6-[(phenylmethoxy)carbonyl]-(R)-6-[(phenylmethoxy)carbonyl]-L-lysyl]-D-Alanine Phenylmethyl Ester

HRID 2258046
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인쇄 미리보기

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HRID 2258046 반응식
[C:1]1([CH2:7][O:8][C:9](=[O:23])[C@@H:10]([C@@H:20]([CH3:22])[OH:21])[NH:11][C:12](=[O:19])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:24](Cl)(Cl)=[O:25].[C:28]1([CH2:34][O:35][C:36](=[O:69])[C@@H:37]([CH3:68])[NH:38][C:39](=[O:67])[C@@H:40]([CH2:42][CH2:43][CH2:44][CH:45]([C:57]([O:59][CH2:60][C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)=[O:58])[NH:46][C:47]([O:49][CH2:50][C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)=[O:48])[NH2:41])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C1COCC1.CC#N.CCOC(C)=O.O>[C:28]1([CH2:34][O:35][C:36](=[O:69])[C@@H:37]([CH3:68])[NH:38][C:39](=[O:67])[C@@H:40]([CH2:42][CH2:43][CH2:44][CH:45]([C:57]([O:59][CH2:60][C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)=[O:58])[NH:46][C:47]([O:49][CH2:50][C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)=[O:48])[NH:41][C:24]([O:21][CH:20]([CH3:22])[CH:10]([NH:11][C:12](=[O:19])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[C:9](=[O:23])[O:8][CH2:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[O:25])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 3

HCID 6371PhosgeneHCID 11034596N-(1-oxoheptyl)-D-allo-Threonine Phenylmethyl EsterHCID 67798175HCID 67798175, 화합물

생성물 1

HCID 86749716N-[N2-[[3-oxo-2-[(1-oxoheptyl)amino]-1-methyl-3-(phenylmethoxy)-propoxy]carbonyl]-N6-[(phenylmethoxy)carbonyl]-(R)-6-[(phenylmethoxy)carbonyl]-L-lysyl]-D-Alanine Phenylmethyl Ester

시약·촉매·용매 3

HCID 6342
Acetonitrile
용매
HCID 8028Tetrahydrofuran용매
HCID 22728543Water ethylacetate용매

실험 절차

A solution of 2e-1 (173.6 mg, 0.54 mmol) in THF (Sure/Seal solvent redried over 3 MS, 1.45 mL) is added to excess cold phosgene (1.92M solution in toluene; 1.40 mL, 2.63 mmol), alternately with TEA (81 μl, 0.58 mmol) over a period of 15 min at 0° C. The resulting milky mixture is stirred for an addition 15 min at the same temperature and for 5 h at room temperature. The mixture is degassed with argon for 30 min and stirred under aspirator pressure for 30 min. The residue is treated with a solution of freshly prepared 3b (0.37 mmol) in CH3CN (redried as for THF, 2.9 mL) and then TEA (81 μl, 0.58 mmol), both added all at once. The white slurry is stirred overnight at ambient temperature. The mixture is taken up in EtOAc/H2O and the layers separated. The aq. phase is extracted with EtOAc twice and the combined organic phase is washed with brine, dried, filtered, and evaporated. Purification of the product by chromatography (3×30 cm column, gradient of 2:1-1:2 hexane/EtOAc) gaves a white wax which is identified as 1a-1: NMR δ 0.86 (m, 3 H), 1.11 (d, J=6.4, 3 H), 1.20-1.40 (m, 8 H), 1.42 (d, J=7.3, 3 H), 1.50-1.75 (m, 4 H, with overlapping H2O signal), 1.75-2.05 (br d, 2 H), 2.20 (m, 2 H), 4.15 (br s, 1 H), 4.47 (br s, 1 H), 4.62 (apparent quintet, 1 H), 4.87 (apparent br d, J≃6, 1 H), 5.00-5.20 (m, 9 H), 5.23 (m, 1 H), 5.37 (br d, 1 H), 6.40 (br d, 1 H), 7.33 (m, 20 H), 7.77 (br d, 1 H); MS (HR-FAB) m/z 923.4420 (M+H, calcd. for C51H63N4O12, 923.4442).

후처리

  1. customThe mixture is degassed with argon for 30 min
  2. stirringstirred under aspirator pressure for 30 min
  3. additionThe residue is treated with a solution
  4. stirringThe white slurry is stirred overnight at ambient temperature
  5. customthe layers separated
  6. extractionThe aq. phase is extracted with EtOAc twice
  7. washthe combined organic phase is washed with brine
  8. customdried
  9. filtrationfiltered
  10. customevaporated
  11. customPurification of the product by chromatography (3×30 cm column, gradient of 2:1-1:2 hexane/EtOAc)

출처 및 근거

ORD 기록
ord-a6a526a9baa442d98931292bd556112e
출처 데이터셋
uspto-grants-1997_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US05658945

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