Triethylamine → HCID 178453493, compound

HRID 2294680Notes

Reaction equation

HRID 2294680 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].[C:27]([O:31][C:32]([NH:34][CH2:35][C:36]([S:39]([CH2:42][C@@H:43]([CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[C:44](O)=[O:45])(=[O:41])=[O:40])([CH3:38])[CH3:37])=[O:33])([CH3:30])([CH3:29])[CH3:28].C(N(CC)CC)C.C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O>[CH:15]1([CH2:14][C@H:6]([NH:5][C:3]([C@@H:2]([NH:1][C:44]([C@H:43]([CH2:47][C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=2)[CH2:42][S:39]([C:36]([CH3:37])([CH3:38])[CH2:35][NH:34][C:32](=[O:33])[O:31][C:27]([CH3:30])([CH3:28])[CH3:29])(=[O:40])=[O:41])=[O:45])[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

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86751629HCID 86751629, compoundHCID 178511793(S)-alpha-amino-N-[(1S,2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl]imidazole-4propionamide

Product 1

HCID 178453493HCID 178453493, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 200 mg (0.5 mmol) of (S)-α-amino-N-[(1S,2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl]imidazole-4-propionamide, 197 mg (0.5 mmol) of (S)-α-[[[2-(1-tert-butoxyformamido)-1,1-dimethylethyl]sulphonyl]methyl]hydrocinnamic acid, 56 mg (0.5 mmol) of triethylamine, 89 mg (0.5 mmol) of HOBT and 209 mg (0.5 mmol) of HBTU in 15 ml of dimethylformamide is stirred at room temperature for 4 hours. Thereafter, the reaction mixture is evaporated to dryness in a high vacuum, the residue is taken up in 50 ml of ethyl acetate and washed twice with 20 ml of saturated sodium bicarbonate solution. After drying the organic phase over sodium sulphate the solvent is evaporated under reduced pressure. For purification, the residue (420 mg) is chromatographed on 20 g of silica gel using a 95:5:0.1 mixture of methylene chloride, methanol and ammonia as the eluent. After lyophilization from dioxan/water there is obtained tert-butyl [2-[[(S)-2-[[(S)-1-[[(1S,2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl)carbamoyl]-2-imidazol-4-ylethyl]carbamoyl]-3-phenylpropyl]sulphonyl]-2-methylpropyl]carbamate as a colourless, amorphous powder; MS: 746 (M+H)+.

Workup

  1. customThereafter, the reaction mixture is evaporated to dryness in a high vacuum
  2. washwashed twice with 20 ml of saturated sodium bicarbonate solution
  3. dry with materialAfter drying the organic phase over sodium sulphate the solvent
  4. customis evaporated under reduced pressure
  5. customFor purification
  6. customthe residue (420 mg) is chromatographed on 20 g of silica gel using
  7. additiona 95:5:0.1 mixture of methylene chloride, methanol and ammonia as the eluent

Sources & evidence

ORD record
ord-9f591c17ac15490c824af7878002cfcc
Source dataset
uspto-grants-1997_11
Patent number
US05688946

Reaction notes

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