Triethylamine → HCID 178513193, compound

HRID 2294711Notes

Reaction equation

HRID 2294711 reaction equation
[NH2:1][C@@H:2]([CH2:21][C:22]1[N:23]=[CH:24][NH:25][CH:26]=1)[C:3]([NH:5][C@@H:6]([CH2:14][CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1)[C@@H:7]([OH:13])[C@H:8]([CH:10]1[CH2:12][CH2:11]1)[OH:9])=[O:4].[NH2:27][C:28]([NH2:30])=[NH:29].[S:31](=[CH:34][CH:35]([CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[C:36](O)=[O:37])(=[O:33])=[O:32].C1C=CC2N([OH:55])N=NC=2C=1.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.O1CCOCC1.O>[NH2:29][C:28]([NH2:30])=[NH:27].[CH:15]1([CH2:14][C@H:6]([NH:5][C:3]([C@@H:2]([NH:1][C:36]([CH:35]([CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH2:34][S:31]([OH:33])(=[O:55])=[O:32])=[O:37])[CH2:21][C:22]2[N:23]=[CH:24][NH:25][CH:26]=2)=[O:4])[C@@H:7]([OH:13])[C@H:8]([CH:10]2[CH2:11][CH2:12]2)[OH:9])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86751649(RS)-alpha-(sulphonylmethyl)hydrocinnamic acid guanidine saltHCID 178511793(S)-alpha-amino-N-[(1S,2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl]imidazole-4propionamide

Product 1

HCID 178513193HCID 178513193, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

A mixture of 200 mg (0.55 mmol) of (S)-α-amino-N-[(1S,2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl]imidazole-4-propionamide, 174 mg (0.57 mmol) of (RS)-α-(sulphonylmethyl)hydrocinnamic acid guanidine salt, 95 mg (0.7 mmol) of HOBT, 62 mg (0.61 mmol) of triethylamine and 231 mg (0.61 mmol) of HBTU in 50 ml of dimethylformamide is stirred at room temperature overnight. Thereafter, the reaction mixture is evaporated to dryness in a high vacuum and, for purification, the crude product obtained is chromatographed on 50 g of silica gel with a 9:1 to 1:1 mixture of water and methanol as the eluent. This chromatography is carried out again in order to separate the two epimers obtained. After lyophilization from dioxan/water there are obtained 81 mg of the less polar (R or S)-2-[[(S)-1-[[(1S,2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl]carbamoyl]-2-imidazol-4-ylethyl]carbamoyl]-3-phenylpropanesulphonic acid guanidine salt and 40 mg of the more polar (S or R)-2-[[(S)-1-[[(1S,2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl]carbamoyl]-2-imidazol-4-ylethyl]carbamoyl]-3-phenylpropanesulphonic acid guanidine salt, each as a colourless powder.

Workup

  1. customThereafter, the reaction mixture is evaporated to dryness in a high vacuum and, for purification
  2. customthe crude product obtained
  3. customis chromatographed on 50 g of silica gel with a 9:1 to 1:1 mixture of water and methanol as the eluent
  4. customto separate the two epimers
  5. customobtained

Sources & evidence

ORD record
ord-4dbd53dcb51143dca552864fdaa921fd
Source dataset
uspto-grants-1997_11
Patent number
US05688946

Reaction notes

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