Triethylamine → HCID 22879396, compound

HRID 2294691Notes

Reaction equation

HRID 2294691 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:12]=[C:11]([CH2:13][C@H:14]([NH:18][C:19](=[O:36])[C@@H:20]([CH2:28][S:29]([C:32]([CH3:35])([CH3:34])[CH3:33])(=[O:31])=[O:30])[CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:15]([OH:17])=O)[N:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:37][C@@H:38]([CH2:46][CH:47]1[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]1)[C@@H:39]([OH:45])[C@H:40]([CH:42]1[CH2:44][CH2:43]1)[OH:41].ON1C(=O)C2C=CC=CC=2N=N1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O>[C:32]([S:29]([CH2:28][C@@H:20]([CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[C:19]([NH:18][C@@H:14]([CH2:13][C:11]1[N:10]=[CH:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH:12]=1)[C:15]([NH:37][C@@H:38]([CH2:46][CH:47]1[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]1)[C@@H:39]([OH:45])[C@H:40]([CH:42]1[CH2:44][CH2:43]1)[OH:41])=[O:17])=[O:36])(=[O:31])=[O:30])([CH3:35])([CH3:33])[CH3:34]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 730263-hydroxy-1,2,3-benzotriazin-4(3H)-oneHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 14930738(1S,2R,3S)-3-amino-4-cyclohexyl-1-cyclopropyl-1,2-butanediolHCID 22862631HCID 22862631, compound

Product 1

HCID 22879396HCID 22879396, compoundYield 151.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 1.98 g (3.06 mmol) of (S)-1-(tert-butoxycarbonyl)-α-[(S)-α-[(tert-butylsulphonyl)methyl]hydrocinnamamido]imidazole-4-propionic acid, 0.58 g (2.55 mmol) of (1S,2R,3S)-3-amino-4-cyclohexyl-1-cyclopropyl-1,2-butanediol, 0.5 g (3.06 mmol) of 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-benzotriazine, 0.42 ml (3.07 mmol) of triethylamine and 1.16 g. (3.06 mmol) of HBTU in 30 ml of dimethylformamide is stirred at room temperature under argon for 2 hours. Subsequently, the dimethylformamide is evaporated in a high vacuum and the residue is taken up in 60 ml of ethyl acetate. The ethyl acetate solution is extracted with 30 ml of cold 2N sodium bicarbonate solution and the aqueous phase is back-extracted twice with 60 ml of ethyl acetate. The combined organic phases are washed in sequence with 30 ml of cold, saturated ammonium chloride solution, 30 ml of cold 2N sodium bicarbonate solution and 30 ml of saturated sodium chloride solution. The organic phase is dried over sodium sulphate and evaporated under reduced pressure. There are obtained 2.82 g of (S)-α-[(S)-α-[(tert-butylsulphonyl)methyl]hydrocinnamamido]-N-[(1S,2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl]-1-Boc-imidazole-4-propionamide as a pale yellow foam.

Workup

  1. customSubsequently, the dimethylformamide is evaporated in a high vacuum
  2. extractionThe ethyl acetate solution is extracted with 30 ml of cold 2N sodium bicarbonate solution
  3. extractionthe aqueous phase is back-extracted twice with 60 ml of ethyl acetate
  4. washThe combined organic phases are washed in sequence with 30 ml of cold, saturated ammonium chloride solution, 30 ml of cold 2N sodium bicarbonate solution and 30 ml of saturated sodium chloride solution
  5. dry with materialThe organic phase is dried over sodium sulphate
  6. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-5990f0dbea0e4b5891905170d4914642
Source dataset
uspto-grants-1997_11
Patent number
US05688946

Reaction notes

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