Diisopropylethylamine → tert-butyl (S)-1-((S)-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxobutan-2-yl(methyl)carbamate

HRID 1055476노트

반응식

HRID 1055476 반응식
Cl.[NH2:2][C@H:3]1[CH2:9][O:8][C:7]2[CH:10]=[CH:11][CH:12]=[CH:13][C:6]=2[N:5]([CH2:14][C:15]2[C:24]3[C:19](=[CH:20][C:21]([Br:25])=[CH:22][CH:23]=3)[CH:18]=[CH:17][C:16]=2[O:26][CH3:27])[C:4]1=[O:28].[C:29]([O:33][C:34]([N:36]([CH3:43])[C@@H:37]([CH2:41][CH3:42])[C:38](O)=[O:39])=[O:35])([CH3:32])([CH3:31])[CH3:30].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[Br:25][C:21]1[CH:20]=[C:19]2[C:24](=[CH:23][CH:22]=1)[C:15]([CH2:14][N:5]1[C:4](=[O:28])[C@@H:3]([NH:2][C:38](=[O:39])[C@@H:37]([N:36]([CH3:43])[C:34](=[O:35])[O:33][C:29]([CH3:30])([CH3:31])[CH3:32])[CH2:41][CH3:42])[CH2:9][O:8][C:7]3[CH:10]=[CH:11][CH:12]=[CH:13][C:6]1=3)=[C:16]([O:26][CH3:27])[CH:17]=[CH:18]2

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 15689337(2S)-2-(((1,1-Dimethylethoxy)carbonyl)methylamino)butanoic acidHCID 118574162(S)-3-amino-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-2,3-dihydrobenzo[b][1,4]oxazepin-4(5H)-one hydrochloride

생성물 1

HCID 131736373tert-butyl (S)-1-((S)-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxobutan-2-yl(methyl)carbamate수율 93%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of (S)-3-amino-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-2,3-dihydrobenzo[b][1,4]oxazepin-4(5H)-one hydrochloride (54 mg, 116 μmol), (S)-2-(tert-butoxycarbonyl(methyl)amino)butanoic acid (27.8 mg, 128 μmol), DIEA (80.6 μl, 466 iumol), and HBTU (48.6 mg, 128 μmol) in DMF (388 μL) was stirred at RT for 30 min. The mixture was diluted with EtOAc, washed with sat. NaHCO3, H2O and brine, then dried over Na2SO4, and filtered. The filtrate was concentrated to give a residue that was purified by silica gel chromatography to provide tert-butyl (S)-1-((S)-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxobutan-2-yl(methyl)carbamate (67.5 mg, 93%) as a white solid. MS m/z 648/650 (MNa)+

후처리

  1. washwashed with sat. NaHCO3, H2O and brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. customto give a residue that
  6. customwas purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-8d4076aa19934a51acee23a75eee7b3e
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394263B2

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