4-Methylmorpholine → N'-phenyloxamide

HRID 1968429Notes

Reaction equation

HRID 1968429 reaction equation
[C:1]1([NH:7][C:8](=[O:12])[C:9](O)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1C[N:16]([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CN1CCOCC1.C(N)(=O)C(N)=O>C(Cl)Cl.C(OCC)(=O)C>[C:1]1([NH:7][C:8](=[O:12])[C:9]([NH2:16])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 10113OxamideHCID 10378Oxanilic acidHCID 2724699PyBOP

Product 1

HCID 596227N'-phenyloxamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Acid 84 (20 mg, 1.4 eq) in CH2Cl2 (1 mL) was treated with PyBOP (53 mg, 1.2 eq) and NMM (0.028 mL, 3.0 eq) and stirred for 5 minutes. To this was added a solution of oxalamide (50 mg, 1.0 eq) and NMM (0.028 mL, 3.0 eq) in CH2Cl2 (1 mL) and the mixture stirred at room temperature overnight. The mixture was diluted with ethyl acetate, the organic phase washed with 0.5N HCl, brine, saturated bicarbonate solution, and brine, then dried over sodium sulfate, filtered and concentrated in vacuo. Purification by preparative HPLC yielded 24 mg (38%) of N-[cyclohexyl-(1-{2-[1-cyclopropylcarbamoyl-hydroxy-methyl)-butylcarbamoyl]-octahydro-indole-1-carbonyl}-2,2-dimethyl-propylcarbamoyl)methyl]-N′-phenyl-oxalamide 96 as a white solid with consistent analytical data. LCMS ret time=4.07, M+H=737.26, M−H=735.22.

Workup

  1. stirringthe mixture stirred at room temperature overnight
  2. washthe organic phase washed with 0.5N HCl, brine, saturated bicarbonate solution, and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-8c08600d570d473495a8be6c8464ad6e
Source dataset
uspto-grants-2013_04
Patent number
US08426359B2

Reaction notes

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