Triethylamine → HCID 86671251, compound

HRID 1952548Notes

Reaction equation

HRID 1952548 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([NH:11][C:12]2[S:13][C:14]([C:18]([OH:20])=O)=[C:15]([CH3:17])[N:16]=2)=[O:10])[CH:5]=[CH:6][CH:7]=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.[CH3:55][C:56]([O:59][C:60]([NH:62][CH2:63][C@H:64]([NH2:69])[C:65]([O:67][CH3:68])=[O:66])=[O:61])([CH3:58])[CH3:57].Cl.C(N(CC)CC)C>CN(C=O)C>[CH3:68][O:67][C:65](=[O:66])[C@@H:64]([NH:69][C:18]([C:14]1[S:13][C:12]([NH:11][C:9](=[O:10])[CH2:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([OH:1])[CH:3]=2)=[N:16][C:15]=1[CH3:17])=[O:20])[CH2:63][NH:62][C:60]([O:59][C:56]([CH3:55])([CH3:58])[CH3:57])=[O:61]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 18334328methyl (2S)-2-amino-3-{[(tert-butoxy)carbonyl]amino}propanoate hydrochlorideHCID 86671249HCID 86671249, compound

Product 1

HCID 86671251HCID 86671251, compoundYield 86.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 2-[2-(3-Hydroxy-phenyl)-acetylamino]-4-methyl-thiazole-5-carboxylic acid (620 mg, 2.121 mmol) in anhydrous DMF (25 mL) was added HBTU (980 mg, 2.584 mmol), HOBt (347 mg, 2.568 mmol), H-DAP(BOC)-OME HCl (810 mg, 3.18 mmol) and triethylamine (1.1 mL, 7.892 mmol). The solution was stirred at 25° C. for 1 h and concentrated at reduced pressure to remove most of the DMF. The reaction was then diluted with ethyl acetate (200 mL), washed with water (50 mL), aqueous 1N HCl (50 mL), and brine (50 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The resulting crude compound was purified by flash chromatography (40%-90% EtOAc in hexanes) to give (S)-3-tert-Butoxycarbonylamino-2-({2-[2-(3-hydroxy-phenyl)-acetylamino]-4-methyl-thiazole-5-carbonyl}-amino)-propionic acid methyl ester (902.1 mg, 77.7%) as a white foam. MS m/e 493.6 (M+H+).

Workup

  1. concentrationconcentrated at reduced pressure
  2. customto remove most of the DMF
  3. additionThe reaction was then diluted with ethyl acetate (200 mL)
  4. washwashed with water (50 mL), aqueous 1N HCl (50 mL), and brine (50 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting crude compound was purified by flash chromatography (40%-90% EtOAc in hexanes)

Sources & evidence

ORD record
ord-0ccc119767a74a9dbcf8d00f57e0b099
Source dataset
uspto-grants-2013_03
Patent number
US08404859B2

Reaction notes

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