Diisopropylethylamine → N-(sec-butoxy)-N-[(2R,3S)-2-hydroxy-3-(3-hydroxy-2-methylanilino)-4-phenylbutyl]-4-methoxybenzenesulfonamide

HRID 29183

Reaction equation

HRID 29183 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]([O:17][CH:18]([CH2:20][CH3:21])[CH3:19])[S:6]([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1)(=[O:8])=[O:7].[OH:30][C:31]1[C:32]([CH3:40])=[C:33]([CH:37]=[CH:38][CH:39]=1)C(O)=O.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(C(C)C)CC)(C)C>CN(C)C=O>[CH:18]([O:17][N:5]([CH2:4][C@@H:3]([OH:22])[C@@H:2]([NH:1][C:33]1[CH:37]=[CH:38][CH:39]=[C:31]([OH:30])[C:32]=1[CH3:40])[CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[S:6]([C:9]1[CH:10]=[CH:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=1)(=[O:7])=[O:8])([CH2:20][CH3:21])[CH3:19]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 2520233-Hydroxy-2-methylbenzoic AcidHCID 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-sulfonamide

Product 1

HCID 21356371N-(sec-butoxy)-N-[(2R,3S)-2-hydroxy-3-(3-hydroxy-2-methylanilino)-4-phenylbutyl]-4-methoxybenzenesulfonamideYield 31.5%

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)(0.12 mmol, 50 mg), 3-hydroxy-2-methylbenzoic acid (0.12 mmol, 18 mg), 1-hydroxybenzotriazole hydrate (0.12 mmol, 16 mg), N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.13 mmol, 25 mg), diisopropylethylamine (0.14 mmol, 0.025 mL) and anhydrous N,N-dimethylformamide (0.5 mL) were combined at room temperature and stirred for 18 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 RPHPLC (water/acetonitrile) and lyophylized providing 20 mg (30%) of a white solid. H1-NMR (CDCl3): δ 7.76-7.73(2H,m), 7.32-7.23 (5H,m), 7.00-6.97 (3H,m), 6.78-6.76 (1H,m), 6.56-6.53 (1H,m), 5.90 (1H,bs), 4.42-4.27 (2H,m), 4.09-3.95 (1H,m), 3.87 (3H,s), 3.25-2.27 (5H,m), 2.05-1.95 (3H,m), 1.77-1.58 (1H,m), 1.55-1.22 (1H,m), 1.24-1.20 (3H,m), 0.93-0.86 (3H,m); MS (ESI): M+H=557.

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 RPHPLC (water/acetonitrile)

Sources & evidence

ORD record
ord-64bc03e834c44c8ea4c35379fe777896
Source dataset
uspto-grants-2008_09
Patent number
US07419967B2

Linked notes

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