Diisopropylethylamine → (2S)-N1-((1S,2R)-1-benzyl-3-sec-butoxy[(4-methoxyphenyl)sulfonyl]amino-2-hydroxypropyl)-2-[(2-quinolinylcarbonyl)amino]butanediamide

HRID 29184Notes

Reaction equation

HRID 29184 reaction equation
[NH2:1][C@@H:2]([CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C@H:3]([OH:22])[CH2:4][N:5](OC(CC)C)[S:6]([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1)(=[O:8])=[O:7].Cl.[NH2:31][C:32](=[O:51])[CH2:33][C@H:34]([NH:38][C:39]([C:41]1[CH:50]=[CH:49][C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[N:42]=1)=[O:40])[C:35]([OH:37])=O.[OH2:52].ON1[C:58]2[CH:59]=[CH:60]C=C[C:57]=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(C(C)C)CC)(C)C>CN(C)C=O>[CH2:23]([C@H:2]([NH:1][C:35](=[O:37])[C@@H:34]([NH:38][C:39]([C:41]1[CH:50]=[CH:49][C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[N:42]=1)=[O:40])[CH2:33][C:32]([NH2:31])=[O:51])[C@@H:3]([OH:22])[CH:4]([NH:5][S:6]([C:9]1[CH:10]=[CH:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=1)(=[O:8])=[O:7])[O:52][CH:58]([CH2:59][CH3:60])[CH3:57])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 57264501N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(sec-butoxy)-4-methoxybenzene-sulfonamideHCID 69220928HCID 69220928, compound

Product 1

HCID 69894616(2S)-N1-((1S,2R)-1-benzyl-3-sec-butoxy[(4-methoxyphenyl)sulfonyl]amino-2-hydroxypropyl)-2-[(2-quinolinylcarbonyl)amino]butanediamideYield 25.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(sec-butoxy)-4-methoxybenzenesulfon-amide (Step 1, Example 67) (0.114 mmol, 48 mg), (2S)-4-amino-4-oxo-2-((2-quinolinylcarbonyl)amino]butanoic acid hydrochloride (0.136 mmol, 42 mg), 1-hydroxybenzotriazole hydrate (0.136 mmol, 19 mg), N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.148 mmol, 28 mg), diisopropylethylamine (5.68 mmol, 0.990 mL) and anhydrous N,N-dimethylformamide (0.5 mL) were combined at room temperature and stirred for 15 hours. The crude reaction mixture was concentrated to a residue, dissolved in ethyl acetate, washed with 1N HCl, 5% aq. potassium carbonate solution, brine and dried over magnesium sulfate. The solution was concentrated to a residue, purified by silica gel chromatography (1:1 hexanes/ethyl acetate) and crystallization from ether and hexanes, providing 20 mg (25%) of a pink solid. H1-NMR (CDCl3) δ 9.20-9.18 (1H,m), 8.32-8.30 (1H,m), 8.22-8.16 (2H,m), 7.89-7.87 (1H,m), 7.80-7.76 (3H,m), 7.65-7.61 (1H,m), 7.14-7.11 (2H,m), 7.05-6.97 (6H,m), 5.76-5.64 (1H,bs), 5.49-5.26 (1H,m), 4.94-4.86 (1H,m), 4.36-4.14 (2H,m), 3.99-3.80 (1H,m), 3.86 (3H,s), 3.14 (1H,bs), 2.98-2.71 (5H,m), 2.71-2.59 (1H,m), 1.80-1.52 (1H,m), 1.48-1.30 (1H,m), 1.22-1.14 (3H,m), 0.94-0.80 (3H,m); MS (ESI): M+H=692.

Workup

  1. customwere combined at room temperature
  2. customThe crude reaction mixture
  3. concentrationwas concentrated to a residue
  4. dissolutiondissolved in ethyl acetate
  5. washwashed with 1N HCl, 5% aq. potassium carbonate solution, brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationThe solution was concentrated to a residue
  8. custompurified by silica gel chromatography (1:1 hexanes/ethyl acetate) and crystallization from ether and hexanes

Sources & evidence

ORD record
ord-1cb1513a594d4b1f87756f0052d027ed
Source dataset
uspto-grants-2008_09
Patent number
US07419967B2

Reaction notes

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