Triethylamine → N-[(S)-alpha-[[[1-methyl-1-[methyl-[2-(2-pyridyl)ethyl]carbamoyl]ethyl]sulfonyl]methyl]hydrocinnamoyl]-3-(thiazol-4-yl)-D,L-alanine methyl ester

HRID 275625Notes

Reaction equation

HRID 275625 reaction equation
C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:32][C:33]([S:47]([CH2:50][C@@H:51]([CH2:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)[C:52](O)=[O:53])(=[O:49])=[O:48])([C:35](=[O:46])[N:36]([CH3:45])[CH2:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][N:40]=1)[CH3:34].Cl.Cl.[CH3:64][O:65][C:66](=[O:75])[CH:67]([CH2:69][C:70]1[N:71]=[CH:72][S:73][CH:74]=1)[NH2:68]>C(#N)C>[CH3:64][O:65][C:66](=[O:75])[CH:67]([CH2:69][C:70]1[N:71]=[CH:72][S:73][CH:74]=1)[NH:68][C:52](=[O:53])[C@@H:51]([CH2:50][S:47]([C:33]([CH3:32])([C:35](=[O:46])[N:36]([CH3:45])[CH2:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][N:40]=1)[CH3:34])(=[O:49])=[O:48])[CH2:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 18659475(S)-alpha-[[[1-methyl-1-[methyl-[2-(2-pyridyl)ethyl]carbamoyl]ethyl]sulfonyl]methyl]hydrocinnamic acidHCID 217527263-(4-thiazolyl)-DL-alanine methyl ester dihydrochloride

Product 1

HCID 54195495N-[(S)-alpha-[[[1-methyl-1-[methyl-[2-(2-pyridyl)ethyl]carbamoyl]ethyl]sulfonyl]methyl]hydrocinnamoyl]-3-(thiazol-4-yl)-D,L-alanine methyl esterYield 73.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

0.28 ml (2.1 mmol) of triethylamine and 265 mg (0.7 mmol) of HBTU were added to a solution of 328 mg (0.7 mmol) of (S)-α-[[[1-methyl-1-[methyl-[2-(2-pyridyl)ethyl]carbamoyl]ethyl]sulfonyl]methyl]hydrocinnamic acid and 181 mg (0.7 mmol) 3-(thiazol-4-yl)-D,L-alanine methyl ester dihydrochloride in 7 ml of acetonitrile and the mixture was stirred at room temperature overnight. Evaporation of the solution under reduced pressure and chromatography of the residue on silica gel using a 200:10:1 mixture of methylene chloride, methanol and ammonia as the eluent yielded 309 mg of N-[(S)-α-[[[1-methyl-1-[methyl-[2-(2-pyridyl)ethyl]carbamoyl]ethyl]sulfonyl]methyl]hydrocinnamoyl]-3-(thiazol-4-yl)-D,L-alanine methyl ester as a colourless foam, MS: 601 (M+H)+.

Workup

  1. customEvaporation of the solution under reduced pressure and chromatography of the residue on silica gel using
  2. additiona 200:10:1 mixture of methylene chloride, methanol and ammonia as the eluent

Sources & evidence

ORD record
ord-75033ae462304136aebeab979d96df0c
Source dataset
uspto-grants-1995_02
Patent number
US05393875

Reaction notes

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