1-Hydroxybenzotriazole → HCID 53982657, compound

HRID 1835599Notes

Reaction equation

HRID 1835599 reaction equation
[NH:1]([C:18]([O:20]CC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O)[C@H:2]([C:15]([OH:17])=[O:16])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([O:10]C(C)(C)C)=[CH:6][CH:5]=1.[C:35]1([C:41]2[CH:46]=[C:45]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)[N:44]=[C:43]([O:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58]C(O)=O)[CH:42]=2)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[C:35]1([C:41]2[CH:46]=[C:45]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)[N:44]=[C:43]([O:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][C:18]([NH:1][C@H:2]([C:15]([OH:17])=[O:16])[CH2:3][C:4]3[CH:5]=[CH:6][C:7]([OH:10])=[CH:8][CH:9]=3)=[O:20])[CH:42]=2)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10406292HCID 10406292, compoundHCID 10895791Fmoc-L-Tyr(tBu)-OHHCID 178435178HCID 178435178, compound

Product 1

HCID 53982657HCID 53982657, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a teabag (5×5 cm polypropylene filters, 0.75 μm mesh) was added 0.30 g of Fmoc-Tyr(OtBu)-Wang Resin. The teabag was washed with the following (10 mL/bag): DMF 2×3 min, 20% piperidine in DMF 1×3 min, 20% piperidine in DMF 1×30 min, DCM 8×3 min, and DMF 3×3 min. About 2.5 equivalents of 6-[(4,6-Diphenyl-2-pyridinyl)oxy]-hexanoic acid, five equivalents of each of the following; HBTU, HOBT, diisopropylethylamine(DIEA) and DMF (10 mL/bag) were added. The bag was then shaken overnight for about 18 h. The bag was then washed with the following (10 mL/bag): DMF 3×3 min, DCM 8×3 min. The bag was dried under high vacuum. The contents of the bag was then placed in a small erlenmeyer flask. To the flask was added 10 mL of cleavage cocktail (95% trifluoroacetic acid, 2.5% triisopropylsilane, and 2.5% water). The resin was allowed to sit for 2 h while occasionally being swirled. After each swirl the sides of the flasks were rinsed with additional cocktail until the total volume of cocktail added was 15 mL. After 2 h, the resin was filtered and washed with TFA (2×4 mL). The filtrates were then concentrated to an oil under high vacuum. The oils were then purified by prep HPLC method 2 described above, to give 43.6 mg of N-[6-[(4,6-diphenyl-2-pyridinyl)oxy]-hexanoyl]tyrosine. ESMS: Calcd. For C32H32N2O5, 524.23; Found, 525.4 (M+H)+1

Workup

  1. washThe teabag was washed with the following (10 mL/bag)
  2. customDMF 2×3 min, 20% piperidine in DMF 1×3 min, 20% piperidine in DMF 1×30 min, DCM 8×3 min, and DMF 3×3 min
  3. washThe bag was then washed with the following (10 mL/bag)
  4. customDMF 3×3 min, DCM 8×3 min
  5. customThe bag was dried under high vacuum
  6. customThe contents of the bag was then placed in a small erlenmeyer flask
  7. additionTo the flask was added 10 mL of cleavage cocktail (95% trifluoroacetic acid, 2.5% triisopropylsilane, and 2.5% water)
  8. waitto sit for 2 h
  9. washAfter each swirl the sides of the flasks were rinsed with additional cocktail until the total volume of cocktail
  10. additionadded
  11. waitAfter 2 h
  12. filtrationthe resin was filtered
  13. washwashed with TFA (2×4 mL)
  14. concentrationThe filtrates were then concentrated to an oil under high vacuum
  15. customThe oils were then purified by prep HPLC method 2

Sources & evidence

ORD record
ord-a747c7c37b704cedabf93b88c38b85b6
Source dataset
uspto-grants-2004_08
Patent number
US06770259B2

Reaction notes

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