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

HRID 1055439
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HRID 1055439 반응식
N#N.Br[C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[C:10]([CH2:14][N:15]1[C:21](=[O:22])[C@@H:20]([NH:23][C:24](=[O:36])[C@@H:25]([N:27]([CH3:35])[C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH3:26])[CH2:19][O:18][C:17]3[CH:37]=[CH:38][CH:39]=[CH:40][C:16]1=3)=[C:9]([O:41][CH3:42])[CH:8]=[CH:7]2.[CH:43]1(B(O)O)[CH2:45][CH2:44]1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:43]1([C:4]2[CH:5]=[C:6]3[C:11](=[CH:12][CH:13]=2)[C:10]([CH2:14][N:15]2[C:21](=[O:22])[C@@H:20]([NH:23][C:24](=[O:36])[C@@H:25]([N:27]([CH3:35])[C:28](=[O:34])[O:29][C:30]([CH3:31])([CH3:32])[CH3:33])[CH3:26])[CH2:19][O:18][C:17]4[CH:37]=[CH:38][CH:39]=[CH:40][C:16]2=4)=[C:9]([O:41][CH3:42])[CH:8]=[CH:7]3)[CH2:45][CH2:44]1
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참가 물질

8

반응물 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 2760897Cyclopropylboronic acidHCID 72713381tert-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-oxopropan-2-yl(methyl)carbamate

생성물 1

HCID 131736358
tert-butyl (S)-1-((S)-5-((6-cyclopropyl-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate
수율 12.8%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

For a duration of 5 min., N2 was bubbled through a mixture of 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-oxopropan-2-yl(methyl)carbamate (200 mg, 327 μmol, Eq: 1.00), cyclopropylboronic acid (33.7 mg, 392 μmol, Eq: 1.20), Na2CO3 (408 μl, 816 μmol, Eq: 2.50) in 1,4-dioxane (2 mL) then Pd(Ph3P)4 (18.9 mg, 16.3 μmol, Eq: 0.05) was added. The mixture was heated to reflux overnight, cooled and diluted with EtOAc. The mixture was washed with water, brine, dried over Na2SO4 and concentrated to give tert-butyl (S)-1-((S)-5-((6-cyclopropyl-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (24 mg, 41.8 μmol, 12.8%) which was used without purification.

후처리

  1. temperatureThe mixture was heated
  2. temperatureto reflux overnight
  3. temperaturecooled
  4. washThe mixture was washed with water, brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated

출처 및 근거

ORD 기록
ord-ed5c9458376244ad83737e872952a25e
출처 데이터셋
uspto-grants-2016_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09394263B2

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