Triethylamine → HCID 86671250, compound

HRID 1952549Notes

Reaction equation

HRID 1952549 reaction equation
[CH3:1][O:2][C:3](=[O:34])[C@@H:4]([NH:14][C:15]([C:17]1[S:21][C:20]([NH:22][C:23](=[O:32])[CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([OH:31])[CH:26]=2)=[N:19][C:18]=1[CH3:33])=[O:16])[CH2:5][NH:6][C:7]([O:9]C(C)(C)C)=O.O1[CH2:40][CH2:39]OCC1.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.[F:75][C:76]1[CH:77]=C(C=[C:83]([F:85])[CH:84]=1)C(O)=O.C(N(CC)CC)C>Cl.CN(C=O)C.C(OCC)C>[CH3:1][O:2][C:3](=[O:34])[C@@H:4]([NH:14][C:15]([C:17]1[S:21][C:20]([NH:22][C:23](=[O:32])[CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([OH:31])[CH:26]=2)=[N:19][C:18]=1[CH3:33])=[O:16])[CH2:5][NH:6][C:7](=[O:9])[C:40]1[CH:39]=[C:83]([F:85])[CH:84]=[C:76]([F:75])[CH:77]=1

Participants

10

Reactant 6

HCID 8471TriethylamineHCID 312751,4-DioxaneHCID 757711-HydroxybenzotriazoleHCID 1012653,5-Difluorobenzoic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86671251HCID 86671251, compound

Product 1

HCID 86671250HCID 86671250, compoundYield 57%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A solution of (S)-3-tert-Butoxycarbonylamino-2-({2-[2-(3-hydroxy-phenyl)-acetylamino]-4-methyl-thiazole-5-carbonyl}-amino)-propionic acid methyl ester (150 mg, 0.305 mmol) in 4M HCl in dioxane (6 mL, 24 mmol) was stirred at 25° C. for 2 h. The reaction mixture was concentrated under reduced pressure. To the reaction solid was added ethyl ether (2×50) followed by concentrating under reduced pressure to give a white solid, which was dissolved in the anhydrous DMF (6 mL). To this solution was added HBTU (174 mg, 0.459 mmol), HOBt (61 mg, 0.451 mmol), 3,5-difluorobenzoic acid (60 mg, 0.379 mmol) and triethylamine (0.16 mL, 1.148 mmol). The solution was allowed to stir at 25° C. for 2 h and concentrated under reduced pressure to remove most of the DMF. The reaction was then diluted with ethyl acetate (100 mL), washed with water (20 mL), followed by aqueous 1N HCl (20 mL) and then brine (20 mL). The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The resulting crude compound was purified by flash chromatography (40%-100% EtOAc in hexanes) to give (S)-3-(3,5-Difluoro-benzoylamino)-2-({2-[2-(3-hydroxy-phenyl)-acetylamino]-4-methyl-thiazole-5-carbonyl}-amino)-propionic acid methyl ester (92.5 mg, 57%) as a white foam. MS m/e 533.5 (M+H+).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customTo the reaction solid
  3. concentrationby concentrating under reduced pressure
  4. customto give a white solid, which
  5. concentrationconcentrated under reduced pressure
  6. customto remove most of the DMF
  7. additionThe reaction was then diluted with ethyl acetate (100 mL)
  8. washwashed with water (20 mL)
  9. dry with materialThe organic layer was dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe resulting crude compound was purified by flash chromatography (40%-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-53c92bc4639a4c83b662a293a96ec297
Source dataset
uspto-grants-2013_03
Patent number
US08404859B2

Reaction notes

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