1-Hydroxybenzotriazole → Benzyl (S)-3-(4-methoxyphenyl)-2-((S)-2-(2-morpholinoacetamido)propanamido)propanoate

HRID 58804

Reaction equation

HRID 58804 reaction equation
[NH2:1][C@@H:2]([CH3:26])[C:3]([NH:5][C@@H:6]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1)[C:7]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8])=[O:4].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.[O:61]1[CH2:66][CH2:65][N:64]([CH2:67][C:68](O)=[O:69])[CH2:63][CH2:62]1.CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>CN(C=O)C>[CH3:25][O:24][C:21]1[CH:20]=[CH:19][C:18]([CH2:17][C@H:6]([NH:5][C:3](=[O:4])[C@@H:2]([NH:1][C:68](=[O:69])[CH2:67][N:64]2[CH2:65][CH2:66][O:61][CH2:62][CH2:63]2)[CH3:26])[C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])=[CH:23][CH:22]=1

Participants

8

Reactant 6

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 4389684-Morpholineacetic acidHCID 516892Sodium BicarbonateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 130394596(S)-benzyl 2-((S)-2-aminopropanamido)-3-(4-methoxyphenyl)propanoate

Product 1

HCID 117870627Benzyl (S)-3-(4-methoxyphenyl)-2-((S)-2-(2-morpholinoacetamido)propanamido)propanoateYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-benzyl 2-((S)-2-aminopropanamido)-3-(4-methoxyphenyl)propanoate (HCl salt, 21.0 g, 53.5 mmol) in DMF (200 mL) at 0° C. was added HBTU (30.4 g, 80.3 mmol) and HOBt (10.8 g, 80.3 mmol). The mixture was stirred for 5 min then 2-morpholinoacetic acid (8.15 g, 56.2 mmol) and DIEA (46.5 mL, 214 mmol) were added. The reaction mixture was stirred at ambient temperature for 30 min. Saturated aqueous NaHCO3 (200 mL) was then added and the resulting mixture was extracted with EtOAc (300 mL×2). The combined extracts were washed with brine (400 mL), dried over anhydrous sodium sulfate, and concentrated. Purification of the residue by flash column chromatography on silica gel (heptane to EtOAc/heptane=3:2) afforded (S)-benzyl 3-(4-methoxyphenyl)-2-((S)-2-(2-morpholinoacetamido)propanamido)propanoate (23.0 g, 89% yield) as a colorless solid.

Workup

  1. stirringThe reaction mixture was stirred at ambient temperature for 30 min
  2. extractionthe resulting mixture was extracted with EtOAc (300 mL×2)
  3. washThe combined extracts were washed with brine (400 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customPurification of the residue by flash column chromatography on silica gel (heptane to EtOAc/heptane=3:2)

Sources & evidence

ORD record
ord-e9ae184a612a46c3a79556cdcc48bb7f
Source dataset
uspto-grants-2016_09
Patent number
US09434761B2

Linked notes

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