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

HRID 630679Notes

Reaction equation

HRID 630679 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][C@H:22]([C:44]([NH:46][CH2:47][C:48]([NH2:50])=[O:49])=[O:45])[CH2:23][S:24][C:25]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[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][C@H:22]([C:44]([NH:46][CH2:47][C:48]([NH2:50])=[O:49])=[O:45])[CH2:23][S:24][C:25]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)=[O:20])=[O:53])([CH3:58])([CH3:57])[CH3:56]

Participants

6

Reactant 3

HCID 284Formic AcidHCID 8471TriethylamineHCID 89554995N-{(2S)-4-{[(4-{(2S)-3-(Allyloxy)-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl}phenoxy)-carbonyl]amino}-2-[(tert-butoxycarbonyl)amino]butanoyl}-S-trityl-L-cysteinylglycinamide

Product 1

HCID 71557575N-[(2S)-2-[(tert-Butoxycarbonyl)amino]-4-{[(4-{(2S)-2-[(tert-butoxycarbonyl)amino]-2-carboxyethyl}phenoxy)carbonyl]amino}butanoyl]-S-trityl-L-cysteinylglycinamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

60 mg (0.031 mmol) of the compound from example 16A was dissolved in approx. 3 ml tetrahydrofuran. 22 μl (0.16 mmol) Triethylamine, 6 μl (0.16 mmol) formic acid and 4 mg (0.003 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 26 mg (86% 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 26 mg (86% of theory) product

Sources & evidence

ORD record
ord-b82117382e444974bb20eac84c1cf340
Source dataset
uspto-grants-2016_04
Patent number
US09315543B2

Reaction notes

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