4-Methylmorpholine → HCID 57041032, compound

HRID 2119764Notes

Reaction equation

HRID 2119764 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.C1C=CC2N([OH:20])N=NC=2C=1.CN1[CH2:27][CH2:26][O:25]CC1.[CH2:28]1[CH2:33]CC(N=C=NC2CCCCC2)C[CH2:29]1>C1COCC1>[S:3]1[C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=[C:2]1[NH:1][C:26](=[O:25])[C@@H:27]([OH:20])[CH:28]([CH3:33])[CH3:29]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 8706Benzo(d)thiazol-2-amineHCID 10868DicyclohexylcarbodiimideHCID 757711-Hydroxybenzotriazole

Product 1

HCID 57041032HCID 57041032, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of (S)-(+)-Hiva (3, 1.00 g, 8.5 mmol), 2-aminobenzothiazole (6q, 1.27 g, 8.5 mmol) and HOBt (2.29 g, 17 mmol, 2 eq) in dry THF (15 ml) is cooled to 0° C., under N2, with stirring. To the solution is added NMM (0.93 mL, 8.5 mmol) and a solution of DCC (1.75 g, 8.5 mmol) in THF (5 mL). The reaction is then allowed to reach room temperature over 2 hours. The solution is filtered and concentrated to dryness. The oily residue is dissolved in CH2Cl2 (50 mL) and washed successively with saturated NaHCO3 solution (50 mL), H2O (50 mL), 10% citric acid solution (50 mL), and H2O (2×50 mL). The organic extract is then dried and the solvent evaporated under reduced pressure to give a crude white solid. Urea by-product is removed by repeated precipitations from ice-cold EtOAc, and the product is recrystallized (three times) from acetone-heptane to give the pure amide as colorless microcrystalline needles (1.8 g, 85%). mp 184.1-184.2° C.; Rf 0.59 (CH2Cl2-EtOAc, 4:1); [α]24D −69.3° (c=1.0); MS m/z 250 (9, M+), 151 (14), 150 (100), 123 (8), 96 (7), 82 (21), 80 (21), 73 (6), 55 (13); 1H NMR (300 MHz, CDCl3) δ 0.97 (d, J=6.9 Hz, 3H, Val CH3), 1.23 (d, J=6.9 Hz, 3H, Val CH3), 2.45 (spd, J1=6.9 Hz, J2=3.0 Hz, 1H, Hiva CHβ), 4.41 (bt, J=3.0 Hz, 1H, Hiva CHα), 5.00 (bd, J=3.9 Hz, 1H, OH), 7.35 (t, J=8.4 Hz, 1H, ArH), 7.47 (t, J=8.4 Hz, 1H, ArH), 7.76 (d, J=8.4 Hz, 1H, ArH), 7.85 (d, J=7.5 Hz, 1H, ArH), 10.55 (bs, 1H, NH). Anal. Calcd. For C12H14N2O2S: C, 57.78; H, 5.64; N, 11.9. Found: C, 57.90; H, 5.87; N, 10.89.

Workup

  1. filtrationThe solution is filtered
  2. concentrationconcentrated to dryness
  3. dissolutionThe oily residue is dissolved in CH2Cl2 (50 mL)
  4. washwashed successively with saturated NaHCO3 solution (50 mL), H2O (50 mL), 10% citric acid solution (50 mL), and H2O (2×50 mL)
  5. extractionThe organic extract
  6. customis then dried
  7. customthe solvent evaporated under reduced pressure
  8. customto give a crude white solid
  9. customUrea by-product is removed
  10. customprecipitations from ice-cold EtOAc
  11. customthe product is recrystallized (three times) from acetone-heptane

Sources & evidence

ORD record
ord-08e484c01e0f40188771df1c6c4f42be
Source dataset
uspto-grants-2004_02
Patent number
US06686445B1

Reaction notes

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