Triethylamine → HCID 88898037, compound

HRID 1952559Notes

Reaction equation

HRID 1952559 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[S:10][C:11]([C:18]([OH:20])=O)=[C:12]([C:14]([F:17])([F:16])[F:15])[N:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].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:11]1[S:10][C:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[N:13][C:12]=1[C:14]([F:15])([F:16])[F: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 534234792-[(tert-Butoxycarbonyl)amino]-4-(trifluoromethyl)-1,3-thiazole-5-carboxylic acid

Product 1

HCID 88898037HCID 88898037, compoundYield 78.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-tert-Butoxycarbonylamino-4-trifluoromethyl-thiazole-5-carboxylic acid (6.23 g, 19.96) in anhydrous DMF (100 mL) was added HBTU (8.29 g, 24.97 mmol), HOBt (3.39 g, 19.96 mmol), H-DAP(BOC)-OME HCL (8.08 g, 31.02 mmol) and triethylamine (11.97 mL, 85.94 mmol). The reaction mixture was stirred at 25′C for 1 h and concentrated under reduced pressure to remove most of the DMF. The residue was diluted with ethyl acetate (200 mL), washed with 1:1 water/brine (40 mL), aqueous 1N HCl (40 mL), brine (40 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The resulting crude compound was purified by flash chromatography (40% to 100% EtOAc in hexanes) to give (S)-3-tert-Butoxycarbonylamino-2-[(2-tert-butoxycarbonylamino-4-trifluoromethyl-thiazole-5-carbonyl)-amino]-propionic acid methyl ester (8 g, 78%) as a pale yellow foam. MS m/e 513.5 (M+H+).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customto remove most of the DMF
  3. additionThe residue was diluted with ethyl acetate (200 mL)
  4. washwashed with 1:1 water/brine (40 mL), aqueous 1N HCl (40 mL), brine (40 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% to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-1651e58596c14467896095ec75ae2d8e
Source dataset
uspto-grants-2013_03
Patent number
US08404859B2

Reaction notes

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