Triethylamine → HCID 68226698, compound

HRID 1952645Notes

Reaction equation

HRID 1952645 reaction equation
FC(F)(F)C(O)=O.[CH3:8][O:9][C:10](=[O:35])[C@@H:11]([NH:14][C:15]([C:17]1[S:18][C:19]([C:23](=[O:34])[NH:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([F:32])=[C:28]([OH:33])[CH:27]=2)=[CH:20][C:21]=1[CH3:22])=[O:16])[CH2:12][NH2:13].C(N(CC)CC)C.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.[S:77]1[CH:81]=[CH:80][CH:79]=[C:78]1[C:82](O)=[O:83]>CN(C=O)C.CCOC(C)=O>[CH3:8][O:9][C:10](=[O:35])[C@@H:11]([NH:14][C:15]([C:17]1[S:18][C:19]([C:23](=[O:34])[NH:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([F:32])=[C:28]([OH:33])[CH:27]=2)=[CH:20][C:21]=1[CH3:22])=[O:16])[CH2:12][NH:13][C:82]([C:78]1[S:77][CH:81]=[CH:80][CH:79]=1)=[O:83]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 107002-Thiophenecarboxylic acidHCID 757711-HydroxybenzotriazoleHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68227405HCID 68227405, compound

Product 1

HCID 68226698HCID 68226698, compoundYield 4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-3-Amino-2-{[5-(4-fluoro-3-hydroxy-benzylcarbamoyl)-3-methyl-thiophene-2-carbonyl]-amino}-propionic acid methyl ester trifluoro-acetic acid salt (0.73 mmol) in anhydrous DMF (15 mL) was added triethylamine (0.31 mL, 2.19 mmol), HBTU (0.33 g, 0.88 mmol), HOBt (0.12 g, 0.88 mmol), and 2-Thiophenecarboxylic acid (0.098 g, 0.77 mmol). The mixture was stirred at room temperature 15 h, treated with EtOAc (50 mL), washed with brine, dried over sodium sulfate, filtered and evaporated. The solid residue was purified by column (30-100% EtOAc in hexane). Material off the column was determined to be the mixed ester. It was refluxed in MeOH (20 ml) containing a catalytic amount of pTsOH for 15 h, purified by column (60-75% EtOAc in hexane). to give 0.014 g (4%) colorless oil. MS m/e 519.9 (M+H+).

Workup

  1. washwashed with brine
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customThe solid residue was purified by column (30-100% EtOAc in hexane)
  6. temperatureIt was refluxed in MeOH (20 ml)
  7. additioncontaining a catalytic amount of pTsOH for 15 h
  8. custompurified by column (60-75% EtOAc in hexane)

Sources & evidence

ORD record
ord-f6ec8d831a404cea93997ad65820cc7d
Source dataset
uspto-grants-2013_03
Patent number
US08404859B2

Reaction notes

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