Formic Acid → N-(tert-Butoxycarbonyl)-O-{[(3S)-3-[(tert-butoxycarbonyl)amino]-4-oxo-4-{[2-(tritylsulfanyl)-ethyl]amino}butyl]carbamoyl}-L-tyrosine

HRID 630678Notes

Reaction equation

HRID 630678 reaction equation
C([O:4][C:5](=[O:62])[C@H:6]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23](=[O:61])[NH:24][CH2:25][CH2:26][C@H:27]([NH:53][C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[C:28](=[O:52])[NH:29][CH2:30][CH2:31][S:32][C:33]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[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>[C:11]([O:10][C:8]([NH:7][C@H:6]([C:5]([OH:62])=[O:4])[CH2:15][C:16]1[CH:17]=[CH:18][C:19]([O:22][C:23](=[O:61])[NH:24][CH2:25][CH2:26][C@H:27]([NH:53][C:54]([O:56][C:57]([CH3:59])([CH3:58])[CH3:60])=[O:55])[C:28](=[O:52])[NH:29][CH2:30][CH2:31][S:32][C:33]([C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=2)([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)=[CH:20][CH:21]=1)=[O:9])([CH3:12])([CH3:13])[CH3:14]

Participants

6

Reactant 3

HCID 284Formic AcidHCID 8471TriethylamineHCID 117893244Allyl-N-(tert-butoxycarbonyl)-O-{[(3S)-3-[(tert-butoxycarbonyl)amino]-4-oxo-4-{[2-(tritylsulfanyl)ethyl]amino}butyl]carbamoyl}-L-tyrosinate

Product 1

HCID 71557574N-(tert-Butoxycarbonyl)-O-{[(3S)-3-[(tert-butoxycarbonyl)amino]-4-oxo-4-{[2-(tritylsulfanyl)-ethyl]amino}butyl]carbamoyl}-L-tyrosine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

98 mg (0.1 mmol) of the compound from example 15A was dissolved in approx. 4 ml tetrahydrofuran. 70 μl (0.5 mmol) Triethylamine, 19 μl (0.5 mmol) formic acid and 11 mg (0.01 mmol) tetrakis(triphenylphosphin)palladium(0) were added. The reaction mixture was stirred over night at room temperature. The reaction was diluted with approx. 5 ml water and twice extracted with approx. 5 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 67 mg (79% of theory) product.

Workup

  1. extractiontwice extracted with approx. 5 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 67 mg (79% of theory) product

Sources & evidence

ORD record
ord-7452d2bea8304b4488fdc607a81c73c0
Source dataset
uspto-grants-2016_04
Patent number
US09315543B2

Reaction notes

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