Formic Acid → 3-[(tert-Butoxycarbonyl)amino]-N-[(4-{(2S)-2-[(tert-butoxycarbonyl)amino]-2-carboxyethyl}-phenoxy)carbonyl]-L-alanyl-S-trityl-L-cysteinamide

HRID 630683Notes

Reaction equation

HRID 630683 reaction equation
C([O:4][C:5](=[O:64])[C@@H:6]([NH:56][C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[CH2:7][C:8]1[CH:55]=[CH:54][C:11]([O:12][C:13]([NH:15][C@H:16]([C:26]([NH:28][C@H:29]([C:51]([NH2:53])=[O:52])[CH2:30][S:31][C:32]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:27])[CH2:17][NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[O:14])=[CH:10][CH:9]=1)C=C.C(N(CC)CC)C.C(O)=O>O1CCCC1.O>[C:22]([O:21][C:19]([NH:18][CH2:17][C@@H:16]([C:26]([NH:28][C@H:29]([C:51]([NH2:53])=[O:52])[CH2:30][S:31][C:32]([C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1)=[O:27])[NH:15][C:13]([O:12][C:11]1[CH:54]=[CH:55][C:8]([CH2:7][C@H:6]([NH:56][C:57]([O:59][C:60]([CH3:61])([CH3:63])[CH3:62])=[O:58])[C:5]([OH:64])=[O:4])=[CH:9][CH:10]=1)=[O:14])=[O:20])([CH3:23])([CH3:24])[CH3:25]

Participants

6

Reactant 3

HCID 284Formic AcidHCID 8471TriethylamineHCID 89545055N-[(4-{(2S)-3-(Allyloxy)-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)carbonyl]-3-[(tert-butoxycarbonyl)amino]-L-alanyl-S-trityl-L-cysteinamide

Product 1

HCID 895447703-[(tert-Butoxycarbonyl)amino]-N-[(4-{(2S)-2-[(tert-butoxycarbonyl)amino]-2-carboxyethyl}-phenoxy)carbonyl]-L-alanyl-S-trityl-L-cysteinamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

2.38 g (2.03 mmol) of the compound from example 25A was dissolved in approx. 35 ml tetrahydrofuran. 1.42 ml (10 mmol) Triethylamine, 0.38 ml (10 mmol) formic acid and 0.24 g (0.20 mmol) tetrakis(triphenylphosphin)palladium(0) were added. The reaction mixture was stirred over night at room temperature. The reaction was diluted with approx. 20 ml water and twice extracted with approx. 30 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. 70 ml silica gel. Solvents used were dichloromethane/methanol 10/1 to dichloromethane/methanol 1/1. The product-containing fractions were combined and concentrated to dryness under reduced pressure to yield 0.72 g (41% of theory) product.

Workup

  1. extractiontwice extracted with approx. 30 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. 70 ml silica gel
  7. concentrationconcentrated to dryness under reduced pressure
  8. customto yield 0.72 g (41% of theory) product

Sources & evidence

ORD record
ord-695d3da873614b6f91bc7c56cc8e4757
Source dataset
uspto-grants-2016_04
Patent number
US09315543B2

Reaction notes

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