Hydrochloric Acid → HCID 88897924, compound

HRID 1952560Notes

Reaction equation

HRID 1952560 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:25]C(C)(C)C)=[O:24])=[N:19][C:18]=1[C:30]([F:33])([F:32])[F:31])=[O:16])[CH2:5][NH:6][C:7](OC(C)(C)C)=[O:8].Cl.O1CCOC[CH2:37]1.CN(C(ON1N=NC2C=C[CH:55]=[CH:56][C:51]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.[S:76]1[CH:80]=[CH:79][CH:78]=[C:77]1C(O)=O.C(N(CC)CC)C>CO.CN(C=O)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:25][C:56]([CH3:55])([CH3:51])[CH3:37])=[O:24])=[N:19][C:18]=1[C:30]([F:31])([F:32])[F:33])=[O:16])[CH2:5][NH:6][C:7]([C:80]1[S:76][CH:77]=[CH:78][CH:79]=1)=[O:8]

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 107002-Thiophenecarboxylic acidHCID 312751,4-DioxaneHCID 757711-HydroxybenzotriazoleHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 88898037HCID 88898037, compound

Product 1

HCID 88897924HCID 88897924, compoundYield 98%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

A stirred solution of (S)-3-tert-Butoxycarbonylamino-2-[(2-tert-butoxycarbonylamino-4-trifluoromethyl-thiazole-5-carbonyl)-amino]-propionic acid methyl ester (10.67 g, 20.82 mmol) in methanol (80 mL) was treated with the 4 M HCl in Dioxane (50 mL, 200 mmol) and reaction was heated at 40° C. for 45 min. The resultant intermediate was concentrated to give a pale yellow foam oil. A solution of this material in DMF (150 mL) was treated with the HBTU (9.6 g, 25.31 mmol), HOBt (3.5 g, 25.90 mmol), 2-thiophenecarboxylic acid (2.9 g, 22.63 mmol) and the triethylamine (19 mL, 136.3 mmol) and stirred at room temp for 2 h. The reaction was then concentrated to remove DMF, followed by dilution with water (300 mL), and extracted with ethyl acetate (1×300 mL, 1×100 mL). The combined organic layers washed with water (3×100 mL) followed by aq sat sodium bicarbonate solution (3×100 mL), water (2×100 mL), brine (100 mL), dried over magnesium sulfate, filtered, concentrated to give (9.41 g) as crude product. Column purification The solid residue was purified by flash column (20-80 EtOAc in hexane) to give 10.2 g (98%) of yellow oil. MS m/e 523.5 (M+H+).

Workup

  1. concentrationThe resultant intermediate was concentrated
  2. customto give a pale yellow foam oil
  3. concentrationThe reaction was then concentrated
  4. customto remove DMF
  5. extractionextracted with ethyl acetate (1×300 mL, 1×100 mL)
  6. washThe combined organic layers washed with water (3×100 mL)
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give (9.41 g) as crude product
  11. customColumn purification The solid residue
  12. customwas purified by flash column (20-80 EtOAc in hexane)

Sources & evidence

ORD record
ord-923cdd4c82f2464eaab19986fe5e68b7
Source dataset
uspto-grants-2013_03
Patent number
US08404859B2

Reaction notes

Loading…