1-Hydroxybenzotriazole → HCID 491689, compound

HRID 1489766Notes

Reaction equation

HRID 1489766 reaction equation
[C:1]([NH:13][C@H:14]([C:19]([OH:21])=O)[CH2:15][C:16](=[O:18])[NH2:17])(=[O:12])[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[CH:22]([N:25]([CH2:34][C@@H:35]([OH:45])[C@@H:36]([NH2:44])[CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])([CH3:24])[CH3:23].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C.C(OCC)(=O)C>[CH:22]([N:25]([CH2:34][C@@H:35]([OH:45])[C@@H:36]([NH:44][C:19](=[O:21])[C@H:14]([CH2:15][C:16](=[O:18])[NH2:17])[NH:13][C:1](=[O:12])[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1)[CH2:37][C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)[NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:31])[CH3:32])=[O:28])([CH3:24])[CH3:23]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 11044384(S)-4-Amino-4-oxo-2-(((quinolin-2-yl)carbonyl)amino)butanoic acidHCID 67551723HCID 67551723, compound

Product 1

HCID 491689HCID 491689, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of the product of Step A (0.111 g; 0.386 mmol), the product of Example 2, Step B (0.13022 g; 0.386 mmol), benzotriazol- 1 -yloxytris (dimethylamino)phosphonium hexafluorophosphate (0.205 g; 0.46 mmol) and 1-hydroxybenzotriazole (0.052 g; 0.384 mmol) in 1 ml of anhydrous DMF was added, N,N-diisopropylethylamine (0.24 ml; 1.38 mmol). After stirring for 12 hours at room temperature the reaction was diluted to 30 ml with ethyl acetate and washed with water, 2% potassium bisulfate, 5% sodium bicarbonate and saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. Evaporation of the solvent under reduced pressure and purification of the residue by column chromatography (silica gel, ethyl acetate) gave 0.152 g (65% yield) of the title product melting at 109°-114° C.; Rf (C)=0.36; Rf (D)=0.37; NMR (CDCl3) 1.0 (m, 6H, val, isopropyl CH3); 1.42 (s, 9H, t-butyl CH3); 2.5-3.1 (m, 7H, asn CH2, butyl CH2 -1,-4, CH-3); 3.44 (m, 1 H, isopropyl CH); 4.21 (m, 1 H, butyl CH-2); 4.55 (s, 1 H, OH); 4.94 (m, 1H, asn CH-α); 5.4-6.2 (m, 3H, amide); 6.7-8.4 (m, 11H, aromatic); 9.25 (m, 1H, NH).

Workup

  1. washwashed with water, 2% potassium bisulfate, 5% sodium bicarbonate and saturated aqueous sodium chloride solution
  2. dry with materialdried over anhydrous magnesium sulfate
  3. customEvaporation of the solvent
  4. customunder reduced pressure and purification of the residue by column chromatography (silica gel, ethyl acetate)

Sources & evidence

ORD record
ord-36af235cfe4e415fa91802948c17997e
Source dataset
uspto-grants-1997_10
Patent number
US05679688

Reaction notes

Loading…