4-Methylmorpholine → HCID 131711195, compound

HRID 2419493Notes

Reaction equation

HRID 2419493 reaction equation
[NH:1]([C:22]([O:24]C(C)(C)C)=O)[C@H:2]([C:7]([NH:9][C@H:10]([C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])[CH3:11])=[O:8])[CH2:3][C:4](=[O:6])[NH2:5].Cl.C1COCC1.CN1CCOCC1.[NH:42]([C:73]([O:75][C:76]([CH3:79])([CH3:78])[CH3:77])=[O:74])[C@H:43](C(OC1C(F)=C(F)C(F)=C(F)C=1F)=O)[CH2:44][CH2:45][CH2:46][CH2:47][NH:48]C(OCC1C=CC=CC=1)=O>CN(C=O)C>[NH:42]([C:73]([O:75][C:76]([CH3:79])([CH3:78])[CH3:77])=[O:74])[C@H:43]([C:22]([NH:1][C@H:2]([C:7]([NH:9][C@H:10]([C:12]([O:14][CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)=[O:13])[CH3:11])=[O:8])[CH2:3][C:4](=[O:6])[NH2:5])=[O:24])[CH2:44][CH2:45][CH2:46][CH2:47][NH2:48]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 14189792HCID 14189792, compoundHCID 18422008HCl tetrahydrofuranHCID 131711194Boc-Asn-Ala-OBzl

Product 1

HCID 131711195HCID 131711195, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Boc-Asn-Ala-OBzl (XXIII) (27.54 g, 70 mmol) was treated with 4 N HCl/THF (875 ml) for 30 minutes at room temperature. Evaporation and treatment with dry ether provided 23.08 g (100%). The hydrochloride salt was dissolved in DMF (250 ml), cooled to 0° C and NMM (4.9 ml, 70 mmol) was added under stirring followed by Boc-Lys(Z)-OPfp (39.5 g, 72.3 mmol). The mixture was stirred for 1 hr at 0° C and 3 hr at room temperature. After evaporation of the solvent to a smaller volume, 0.5 N HCl was added and the precipitated product was collected by filtration and washed on the funnel with H2O, (5%) NaHCO3 and H2O. After drying, it was triturated with EtOAc and then with petroleum ether, yield 41.5 g (90.4%); mp 148°-150° C; [α]D25 -15.3° (c 2, DMF). Anal. Calcd for C33H45N5O9 (655.76): C, 60.44; H, 6.92; N, 10.68. Found: C, 60.50; H, 6.97; N, 10.70.

Workup

  1. customEvaporation and treatment with dry ether
  2. customprovided 23.08 g (100%)
  3. stirringThe mixture was stirred for 1 hr at 0° C and 3 hr at room temperature
  4. customAfter evaporation of the solvent to a smaller volume, 0.5 N HCl
  5. additionwas added
  6. filtrationthe precipitated product was collected by filtration
  7. washwashed on the funnel with H2O, (5%) NaHCO3 and H2O
  8. customAfter drying
  9. customit was triturated with EtOAc

Sources & evidence

ORD record
ord-f91e02f64a1d435db39b5bf4e1e21d06
Source dataset
uspto-grants-1978_08
Patent number
US04105652

Reaction notes

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