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

HRID 630680Notes

Reaction equation

HRID 630680 reaction equation
C([O:4][C:5](=[O:69])[C@@H:6]([NH:61][C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])[CH2:7][C:8]1[CH:60]=[CH:59][C:11]([O:12][C:13]([NH:15][CH2:16][CH2:17][C@H:18]([NH:51][C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[C:19]([NH:21][CH2:22][C:23]([NH:25][C@H:26]([C:48]([NH2:50])=[O:49])[CH2:27][S:28][C:29]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[O:24])=[O:20])=[O:14])=[CH:10][CH:9]=1)C=C.C(N(CC)CC)C.C(O)=O>O1CCCC1.O>[C:55]([O:54][C:52]([NH:51][C@@H: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:61][C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])[C:5]([OH:69])=[O:4])=[CH:60][CH:59]=1)=[O:14])[C:19]([NH:21][CH2:22][C:23]([NH:25][C@H:26]([C:48]([NH2:50])=[O:49])[CH2:27][S:28][C:29]([C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1)([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)=[O:24])=[O:20])=[O:53])([CH3:58])([CH3:57])[CH3:56]

Participants

6

Reactant 3

HCID 284Formic AcidHCID 8471TriethylamineHCID 89545100N-{(2S)-4-{[(4-{(2S)-3-(Allyloxy)-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)-carbonyl]amino}-2-[(tert-butoxycarbonyl)amino]butanoyl}glycyl-S-trityl-L-cysteinamide

Product 1

HCID 89554988N-[(2S)-2-[(tert-Butoxycarbonyl)amino]-4-{[(4-{(2S)-2-[(tert-butoxycarbonyl)amino]-2-carboxyethyl}phenoxy)carbonyl]amino}butanoyl]glycyl-S-trityl-L-cysteinamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

860 mg (0.89 mmol) of the compound from example 19A was dissolved in approx. 20 ml tetrahydrofuran. 620 μl (4.45 mmol) Triethylamine, 168 μl (4.45 mmol) formic acid and 103 mg (0.089 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 purified by preparative RP-HPLC on a C18 column with a water/methanol gradient to yield 329 mg (38% of theory) product.

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. customThe raw product was purified by preparative RP-HPLC on a C18 column with a water/methanol gradient
  6. customto yield 329 mg (38% of theory) product

Sources & evidence

ORD record
ord-0c8106b982b54de1aea7625bc24caaaa
Source dataset
uspto-grants-2016_04
Patent number
US09315543B2

Reaction notes

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