4-Methylmorpholine → HCID 57079954, compound

HRID 1647275Notes

Reaction equation

HRID 1647275 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:14]([OH:16])=O)[CH2:10][C:11](=[O:13])[NH2:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.Cl.Cl.[NH2:29][C@@H:30]([CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C@H:31]([OH:42])[CH2:32][N:33]1[CH2:37][CH2:36][CH2:35][C@H:34]1[C:38]([F:41])([F:40])[F:39].CN1CCOCC1>CN(C=O)C>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:14]([NH:29][C@@H:30]([CH2:43][C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1)[C@H:31]([OH:42])[CH2:32][N:33]1[CH2:37][CH2:36][CH2:35][C@H:34]1[C:38]([F:41])([F:39])[F:40])=[O:16])[CH2:10][C:11](=[O:13])[NH2:12])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 82035N2-((tert-Butoxy)carbonyl)-L-asparagineHCID 86748769HCID 86748769, compound

Product 1

HCID 57079954HCID 57079954, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A stirred solution of 731 mg (3.12 mmol) of N-(tert-butoxycarbonyl)-L-asparagine in 6 ml of anhydrous DMF was treated at 0° C. with 530 mg (3.44 mmol) of HOBT and 1.39 g (3.28 mmol) of CMTC. A solution of 1,114 mg (2.84 mmol) of the compound from Example 3 and 1.6 ml (14.20 retool) of N-methylmorpholine in 8 ml of DMF was then added. The cooling bath was removed and the mixture was stirred at room temperature for 3 h. It was then concentrated in vacuo and the residue was partitioned between 40 ml of ethyl acetate and 40 ml of water. The water phase was extracted with 10 ml of ethyl acetate, and the combined extracts were washed with 50 ml of water and dried over MgSO4. After evaporation of the solvent in vacuo and chromatography of the crude product on 200 g of silica gel (dichloromethane:methanol 9:1), 1.42 g (89% of theory) of the title compound were obtained as crystals. Melting points: 104° C. Rf =0.15, I(9:1) MS(FAB): m/e=517 (M+H)+

Workup

  1. customThe cooling bath was removed
  2. concentrationIt was then concentrated in vacuo
  3. customthe residue was partitioned between 40 ml of ethyl acetate and 40 ml of water
  4. extractionThe water phase was extracted with 10 ml of ethyl acetate
  5. washthe combined extracts were washed with 50 ml of water
  6. dry with materialdried over MgSO4
  7. customAfter evaporation of the solvent in vacuo and chromatography of the crude product on 200 g of silica gel (dichloromethane:methanol 9:1), 1.42 g (89% of theory) of the title compound
  8. customwere obtained as crystals
  9. custom104° C

Sources & evidence

ORD record
ord-6dae34a0264b4f2881da2525af767e7c
Source dataset
uspto-grants-1995_07
Patent number
US05430151

Reaction notes

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