Triethylamine → HCID 178445995, compound

HRID 1030202Notes

Reaction equation

HRID 1030202 reaction equation
[CH3:1][C:2]([NH:5][C:6](=[O:19])[CH2:7][C@@H:8]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:9]([OH:11])=O)([CH3:4])[CH3:3].C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:54][C@H:55]([C:62]([NH:64][C@@H:65]([CH2:73][CH:74]([CH3:76])[CH3:75])[C@H:66]([C:68]1[S:69][CH:70]=[CH:71][N:72]=1)[OH:67])=[O:63])[CH2:56][C:57]1[N:61]=[CH:60][NH:59][CH:58]=1>ClCCl>[C:13]1([CH2:12][C@H:8]([CH2:7][C:6]([NH:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:19])[C:9]([NH:54][C@H:55]([C:62]([NH:64][C@@H:65]([CH2:73][CH:74]([CH3:76])[CH3:75])[C@H:66]([C:68]2[S:69][CH:70]=[CH:71][N:72]=2)[OH:67])=[O:63])[CH2:56][C:57]2[N:61]=[CH:60][NH:59][CH:58]=2)=[O:11])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 22843415HCID 22843415, compoundHCID 178446016HCID 178446016, compound

Product 1

HCID 178445995HCID 178445995, compoundYield 111.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-10 °C

Procedure

To 0.276 g of (R)alpha-[2-[(1,1-dimethylethyl)amino]2-oxoethyl]benzenepropionic acid in one ml of dichloromethane was added 0.014 ml of triethylamine and 0.465 g of benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP). After 1.5 minutes, 0.337 g of N-(L-histidyl)-(S)2-amino-4-methyl-(R)1-(2-thiazolyl)pentan-1-ol was added and one ml of dichloromethane. The mixture was stirred 16 hours and the solvent removed. The residue in 5 ml of ethyl acetate was washed with 2 ml of water, three times with 2 ml of 1M sodium bicarbonate with 2 ml of brine. Cooling (-10° C.) gave crystals which were filtered off. The filtrate was concentrated under vacuum to give 0.65 g of an oil. This oil was purified by thick layer chromatography on five 20×20×0.2cm silica gel plates developed with 20% methanol in dichloromethane containing 0.2% triethylamine. The band at RF 0.8 was separated, washed with methanol and the solvent removed. The residue in dichloromethane was filtered and the filtrate concentrated to give 0.3 g of a glass, mp 120°-130° C. [α]D26 -8°±1(c, 1.042, methanol).

Workup

  1. customthe solvent removed
  2. washThe residue in 5 ml of ethyl acetate was washed with 2 ml of water, three times with 2 ml of 1M sodium bicarbonate with 2 ml of brine
  3. customgave crystals which
  4. filtrationwere filtered off
  5. concentrationThe filtrate was concentrated under vacuum

Sources & evidence

ORD record
ord-0ea4a2f0395f49db9861495e43503bb7
Source dataset
uspto-grants-1992_04
Patent number
US05104869

Reaction notes

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