Diisopropylethylamine → HCID 123324359, compound

HRID 588922Notes

Reaction equation

HRID 588922 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:15]([OH:17])=O)[CH2:10][O:11][C:12]#[C:13][CH3:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:19][O:20][C:21](=[O:24])[CH2:22][NH2:23].C(N(CC)C(C)C)(C)C.C1C=C2N=NN(O)C2=CC=1.O.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[CH3:19][O:20][C:21](=[O:24])[CH2:22][NH:23][C:15](=[O:17])[C@H:9]([CH2:10][O:11][C:12]#[C:13][CH3:14])[NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 122755Glycine methyl ester hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 87404101HCID 87404101, compound2×

Product 1

HCID 123324359HCID 123324359, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

N-tert-butoxycarbonyl O-propynyl L-serine (14.55 g, 59.82 mmol) was dissolved in DMF (60 mL) and the solution cooled to 0° C. (icebath). Glycine methyl ester hydrochloride (7.51 g, 59.8 mmol) was suspended in DMF (40 mL) and N,N-diisopropylethylamine (7.73 g, 59.8 mmol) added. The resulting suspension was added to the solution of N-tert-butoxycarbonyl O-propynyl L-serine in one portion. HOBt hydrate (9.16 g, 59.8 mmol) dissolved in DMF (20 mL) was added. Finally, EDC hydrochloride (12.61 g, 65.8 mmol) was added in small portions. The reaction mixture was stirred for 1 h at 0° C. after which the icebath was removed and stirring continued for 25 h at room temperature before the solvent was evaporated. The residue was taken up in EtOAc (400 mL) and the solution washed with 1 M aqueous H2SO4 (3×200 mL), 7.5% (w/w) K2CO3 solution (3×200 mL) and saturated brine (200 mL). The solution was dried with anhydrous MgSO4 and the solvent evaporated affording a yellow/orange oil (17.23 g, 92%); δH (300 MHz; d6-DMSO) 8.31 (1H, t, J 6, NH(Gly)), 6.85 (1H, d, J 8, NH(propSer)), 4.26-4.15 (1H, m, CαH(propSer)), 4.13 (2H, t, J 2, CH2CCH), 3.88 (1H, dd, J 17 and 6, CαHH(Gly)), 3.81 (1H, dd, J 17 and 6, CαHH(Gly)), 3.65 (1H, dd, J 10 and 5, CHH), 3.62 (3H, s, OCH3), 3.52 (1H, dd, J 10 and 8, CHH), 3.41 (1H, t, J 2, CCH), 1.39 (9H, s, (CH3)3); δC (75 MHz; d6-DMSO) 170.2, 170.0, 155.1, 79.9, 78.3, 77.2, 69.2, 59.7, 57.6, 54.0, 51.6, 40.6, 28.1, 20.7, 14.0

Workup

  1. additionwas added
  2. customwas removed
  3. stirringstirring
  4. waitcontinued for 25 h at room temperature before the solvent
  5. customwas evaporated
  6. washthe solution washed with 1 M aqueous H2SO4 (3×200 mL), 7.5% (w/w) K2CO3 solution (3×200 mL) and saturated brine (200 mL)
  7. dry with materialThe solution was dried with anhydrous MgSO4
  8. customthe solvent evaporated

Sources & evidence

ORD record
ord-5144a80a737549db93655c916860b3f3
Source dataset
uspto-grants-2016_01
Patent number
US09227995B2

Reaction notes

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