Water → methyl 3-((2S,3R)-3-hydroxy-4-((5-isopropylpyridin-3-yl)methylamino)-1-phenylbutan-2-ylcarbamoyl)benzoate

HRID 2071190Notes

Reaction equation

HRID 2071190 reaction equation
CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.O.[CH3:24][O:25][C:26]([C:28]1[CH:29]=[C:30]([CH:34]=[CH:35][CH:36]=1)[C:31]([OH:33])=O)=[O:27].[NH2:37][C@@H:38]([CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)[C@H:39]([OH:52])[CH2:40][NH:41][CH2:42][C:43]1[CH:44]=[N:45][CH:46]=[C:47]([CH:49]([CH3:51])[CH3:50])[CH:48]=1.CCN(C(C)C)C(C)C.O1C2C=CC=CC=2C=C1CNC(=O)OC(C)(C)C>C(Cl)Cl>[OH:52][C@H:39]([CH2:40][NH:41][CH2:42][C:43]1[CH:44]=[N:45][CH:46]=[C:47]([CH:49]([CH3:51])[CH3:50])[CH:48]=1)[C@@H:38]([NH:37][C:31]([C:30]1[CH:29]=[C:28]([CH:36]=[CH:35][CH:34]=1)[C:26]([O:25][CH3:24])=[O:27])=[O:33])[CH2:53][C:54]1[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=1

Participants

9

Reactant 7

HCID 962WaterHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 6018803-(Methoxycarbonyl)benzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68671575Tert-butyl benzofuran-2-ylmethylcarbamateHCID 68672432(2R,3S)-3-amino-1-((5-isopropylpyridin-3-yl)methylamino)-4-phenylbutan-2-ol

Product 1

HCID 68671696methyl 3-((2S,3R)-3-hydroxy-4-((5-isopropylpyridin-3-yl)methylamino)-1-phenylbutan-2-ylcarbamoyl)benzoateYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

EDCI.HCl (0.175 g, 0.915 mmol, 1.1 eq) and HOBT.H2O (0.124 g, 0.915 mmol, 1.1 eq) were added to a stirred solution of 3-(methoxycarbonyl)benzoic acid in 5 ml anhydrous CH2Cl2 at 0° C. under Ar. In a separate flask (2R,3S)-3-amino-1-((5-isopropylpyridin-3-yl)methylamino)-4-phenylbutan-2-ol (0.3118 g, 0.832 mmol, 1.1 eq) in 3 ml anhydrous CH2Cl2 under Ar was treated with DIPEA (1.2 ml, 0.86 g, 6.66 mmol, 8 eq). After both solutions had stirred for 1 h, the active ester was treated with the free-base amine. The reaction was stirred at 0° C. to room temperature overnight. The solvent was removed in vacuo. The residue was partitioned between EtOAc/H2O and the layers were separated. The organic layer was washed with water (×3), brine (×1), and dried over Na2SO4. The inorganics were filtered off, and the solvent removed in vacuo. Purification via flash chromatography yielded 0.274 g (0.58 mmol, 69% yield) of methyl 3-((2S,3R)-3-hydroxy-4-((5-isopropylpyridin-3-yl)methylamino)-1-phenylbutan-2-ylcarbamoyl)benzoate.

Workup

  1. stirringThe reaction was stirred at 0° C. to room temperature overnight
  2. customThe solvent was removed in vacuo
  3. customThe residue was partitioned between EtOAc/H2O
  4. customthe layers were separated
  5. washThe organic layer was washed with water (×3), brine (×1)
  6. dry with materialdried over Na2SO4
  7. filtrationThe inorganics were filtered off
  8. customthe solvent removed in vacuo
  9. customPurification via flash chromatography

Sources & evidence

ORD record
ord-74824ab6903a49efb7b09b37fc664b74
Source dataset
uspto-grants-2012_10
Patent number
US08299267B2

Reaction notes

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