Formic Acid → O-({(3S)-4-[(6-{[(2R)-1-Amino-1-oxo-3-(tritylsulfanyl)propan-2-yl]amino}-6-oxohexyl)amino]-3-[(tert-butoxycarbonyl)amino]-4-oxobutyl}carbamoyl)-N-(tert-butoxycarbonyl)-L-tyrosine

HRID 630681Notes

Reaction equation

HRID 630681 reaction equation
C([O:4][C:5](=[O:73])[C@H:6]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23](=[O:72])[NH:24][CH2:25][CH2:26][C@H:27]([NH:64][C:65]([O:67][C:68]([CH3:71])([CH3:70])[CH3:69])=[O:66])[C:28]([NH:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][C:36]([NH:38][C@@H:39]([CH2:43][S:44][C:45]([C:58]2[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=2)([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C:40]([NH2:42])=[O:41])=[O:37])=[O:29])=[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>[NH2:42][C:40](=[O:41])[C@@H:39]([NH:38][C:36](=[O:37])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][NH:30][C:28](=[O:29])[C@@H:27]([NH:64][C:65]([O:67][C:68]([CH3:71])([CH3:70])[CH3:69])=[O:66])[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:73])=[O:4])[NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[CH:21][CH:20]=1)=[O:72])[CH2:43][S:44][C:45]([C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1)([C:58]1[CH:59]=[CH:60][CH:61]=[CH:62][CH:63]=1)[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1

Participants

6

Reactant 3

HCID 284Formic AcidHCID 8471TriethylamineHCID 89554992Allyl-O-({(3S)-4-[(6-{[(2R)-1-amino-1-oxo-3-(tritylsulfanyl)propan-2-yl]amino}-6-oxohexyl)-amino]-3-[(tert-butoxycarbonyl)amino]-4-oxobutyl}carbamoyl)-N-(tert-butoxycarbonyl)-L-tyrosinate

Product 1

HCID 71557729O-({(3S)-4-[(6-{[(2R)-1-Amino-1-oxo-3-(tritylsulfanyl)propan-2-yl]amino}-6-oxohexyl)amino]-3-[(tert-butoxycarbonyl)amino]-4-oxobutyl}carbamoyl)-N-(tert-butoxycarbonyl)-L-tyrosine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

250 mg (0.24 mmol) of the compound from example 22A was dissolved in approx. 5 ml tetrahydrofuran. 170 μl (1.22 mmol) Triethylamine, 48 μl (1.22 mmol) formic acid and 28 mg (0.024 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-bd6afc3fdad44718a1f2bdb9b00ed1a2
Source dataset
uspto-grants-2016_04
Patent number
US09315543B2

Reaction notes

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