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Formic Acid → N2-(tert-Butoxycarbonyl)-N5-[(4-{(2S)-2-[(tert-butoxycarbonyl)amino]-2-carboxyethyl}phenoxy)-carbonyl]-L-ornithyl-S-trityl-L-cysteinamide

HRID 630675
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HRID 630675 반응식
C([O:4][C:5](=[O:66])[C@@H:6]([NH:58][C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])[CH2:7][C:8]1[CH:57]=[CH:56][C:11]([O:12][C:13]([NH:15][CH2:16][CH2:17][CH2:18][C@@H:19]([C:28]([NH:30][C@H:31]([C:53]([NH2:55])=[O:54])[CH2:32][S:33][C:34]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[O:29])[NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[O:14])=[CH:10][CH:9]=1)C=C.C(N(CC)CC)C.C(O)=O>O1CCCC1.O>[C:24]([O:23][C:21]([NH:20][C@H:19]([C:28]([NH:30][C@H:31]([C:53]([NH2:55])=[O:54])[CH2:32][S:33][C:34]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)([C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)=[O:29])[CH2:18][CH2:17][CH2:16][NH:15][C:13]([O:12][C:11]1[CH:10]=[CH:9][C:8]([CH2:7][C@H:6]([NH:58][C:59]([O:61][C:62]([CH3:63])([CH3:65])[CH3:64])=[O:60])[C:5]([OH:66])=[O:4])=[CH:57][CH:56]=1)=[O:14])=[O:22])([CH3:25])([CH3:26])[CH3:27]
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참가 물질

6

반응물 3

HCID 284Formic AcidHCID 8471TriethylamineHCID 89544893N5-[(4-{(2S)-3-(Allyloxy)-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)carbonyl]-N2-(tert-butoxycarbonyl)-L-ornithyl-S-trityl-L-cysteinamide

생성물 1

HCID 89555038N2-(tert-Butoxycarbonyl)-N5-[(4-{(2S)-2-[(tert-butoxycarbonyl)amino]-2-carboxyethyl}phenoxy)-carbonyl]-L-ornithyl-S-trityl-L-cysteinamide

시약·촉매·용매 2

HCID 962Water용매
HCID 8028Tetrahydrofuran용매

실험 절차

3.06 g (2.33 mmol) of the compound from example 10A was dissolved in 46 ml tetrahydrofuran. 1.63 ml (11.6 mmol) triethylamine, 0.44 ml (11.6 mmol) formic acid and 0.265 g (0.233 mmol) tetrakis(triphenylphosphin)palladium(0) were added. The reaction mixture was stirred over night at room temperature. The reaction was diluted with approx. 50 ml water and twice extracted with approx. 50 ml dichloromethane. The combined organic phases were extracted with brine, dried over sodium sulfate and concentrated to dryness under reduced pressure. The raw product was dissolved in dichloromethane and chromatographed over approx. 500 ml silica gel. Solvents used were dichloromethane, dichloromethane/methanol 40/1 and dichloromethane/methanol 1/1. The product-containing fractions were combined and concentrated to dryness under reduced pressure. This gave 1.40 g raw product of 86% purity. The product was further purified by preparative RP-HPLC on a C18 column with a water/methanol gradient to yield 2 fractions: 0.93 g product (45% of theory).

후처리

  1. extractiontwice extracted with approx. 50 ml dichloromethane
  2. extractionThe combined organic phases were extracted with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated to dryness under reduced pressure
  5. dissolutionThe raw product was dissolved in dichloromethane
  6. customchromatographed over approx. 500 ml silica gel
  7. concentrationconcentrated to dryness under reduced pressure
  8. customThe product was further purified by preparative RP-HPLC on a C18 column with a water/methanol gradient
  9. customto yield 2 fractions

출처 및 근거

ORD 기록
ord-a6170f2e77d64e958fc0a4c4c8b1359c
출처 데이터셋
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09315543B2

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