Formic Acid → O-({(14S)-1-Azido-14-[(tert-butoxycarbonyl)amino]-13-oxo-3,6,9-trioxa-12-azahexadecan-16-yl}carbamoyl)-N-(tert-butoxycarbonyl)-L-tyrosine

HRID 630682Notes

Reaction equation

HRID 630682 reaction equation
C([O:4][C:5](=[O:54])[C@H:6]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23](=[O:53])[NH:24][CH2:25][CH2:26][C@H:27]([NH:45][C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[C:28](=[O:44])[NH:29][CH2:30][CH2:31][O:32][CH2:33][CH2:34][O:35][CH2:36][CH2:37][O:38][CH2:39][CH2:40][N:41]=[N+:42]=[N-:43])=[CH:18][CH:17]=1)[NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])C=C.C(N(CC)CC)C.C(O)=O>O1CCCC1.O>[N:41]([CH2:40][CH2:39][O:38][CH2:37][CH2:36][O:35][CH2:34][CH2:33][O:32][CH2:31][CH2:30][NH:29][C:28](=[O:44])[C@@H:27]([NH:45][C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:26][CH2:25][NH:24][C:23]([O:22][C:19]1[CH:18]=[CH:17][C:16]([CH2:15][C@@H:6]([C:5]([OH:54])=[O:4])[NH:7][C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9])=[CH:21][CH:20]=1)=[O:53])=[N+:42]=[N-:43]

Participants

6

Reactant 3

HCID 284Formic AcidHCID 8471TriethylamineHCID 89555031Allyl-O-({(14S)-1-azido-14-[(tert-butoxycarbonyl)amino]-13-oxo-3,6,9-trioxa-12-azahexadecan-16-yl}carbamoyl)-N-(tert-butoxycarbonyl)-L-tyrosinate

Product 1

HCID 71557730O-({(14S)-1-Azido-14-[(tert-butoxycarbonyl)amino]-13-oxo-3,6,9-trioxa-12-azahexadecan-16-yl}carbamoyl)-N-(tert-butoxycarbonyl)-L-tyrosine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

276 mg (0.344 mmol) of the compound from example 23A was dissolved in approx. 15 ml tetrahydrofuran. 235 μl (1.68 mmol) Triethylamine, 63 μl (1.68 mmol) formic acid and 39 mg (0.034 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. 20 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 purified by preparative RP-HPLC on a C18 column with a water/methanol gradient to yield 167 mg (65% of theory) product.

Workup

  1. extractiontwice extracted with approx. 20 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. customThe raw product was purified by preparative RP-HPLC on a C18 column with a water/methanol gradient
  6. customto yield 167 mg (65% of theory) product

Sources & evidence

ORD record
ord-0167495919cb4bc597c9f7dda5640434
Source dataset
uspto-grants-2016_04
Patent number
US09315543B2

Reaction notes

Loading…