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

HRID 630675Notes

Reaction equation

HRID 630675 reaction equation
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]

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-a6170f2e77d64e958fc0a4c4c8b1359c
Source dataset
uspto-grants-2016_04
Patent number
US09315543B2

Reaction notes

Loading…