4-Methylmorpholine → HCID 87349528, compound

HRID 1010479Notes

Reaction equation

HRID 1010479 reaction equation
C[O:2][C:3](=O)[CH2:4][CH:5]1[CH2:10][CH2:9][C@H:8]([C:11](=[O:32])[NH:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[N:24]=[C:23]([CH3:31])[CH:22]=3)=[CH:15][CH:14]=2)[C@@H:7]([C:33](=[O:43])[NH:34][O:35]CC2C=CC=CC=2)[CH2:6]1.C1CN([P+](ON2N=[N:69][C:64]3C=[CH:66][CH:67]=[CH:68][C:63]2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.Cl.C(ON)C1C=CC=CC=1.CN1CCOCC1>CN(C=O)C>[OH:35][NH:34][C:33]([C@H:7]1[CH2:6][CH:5]([CH2:4][C:3](=[O:2])[N:69]2[CH2:66][CH2:67][CH2:68][CH2:63][CH2:64]2)[CH2:10][CH2:9][C@@H:8]1[C:11]([NH:12][C:13]1[CH:14]=[CH:15][C:16]([O:19][CH2:20][C:21]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[N:24]=[C:23]([CH3:31])[CH:22]=2)=[CH:17][CH:18]=1)=[O:32])=[O:43]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 102312Benzyloxyamine hydrochlorideHCID 2724699PyBOPHCID 87349143HCID 87349143, compound

Product 1

HCID 87349528HCID 87349528, compoundYield 93%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Part 8: [3-(S)-Benzyloxycarbamoyl-4-(S)-[4-(2-methyl-quinolin-4-ylmethoxy)-phenylcarbamoyl]-cyclohexyl]-acetic acid methyl ester. To an oven-dried 5 mL conical vial equipped with a magnetic stir bar and under a nitrogen gas atmosphere was placed sequentially: 5-methoxycarbonylmethyl-2-(S)-[4-(2-methylquinolin-4-ylmethoxy)-phenylcarbamoyl]-cyclohexane-(S)-carboxylic acid (212 mg, 0.43 mmol), anhydrous DMF (3 mL), PyBOP reagent (320 mg, 0.61 mmol), O-benzylhydroxylamine hydrochloride (100 mg, 0.627 mmol), and 4-methyl morpholine (0.160 mL, 1.47 mmol). After stirring the reaction mixture overnight, the reaction was quenched with 5% citric acid (1 mL) and the reaction mixture was diluted with ethyl acetate (15 mL) and water (4 mL). The aqueous layer was extracted with ethyl acetate (3×3 mL) and the combined organic phases were washed with saturated sodium bicarbonate (3×5 mL), brine (5 mL), dried (NaSO4), and concentrated in-vacuo. Purification by Combiflash (0 to 15% methanol in methylene chloride over 30 min) to afford 238 mg (93%) of the pure amide. LCMS (ESI): 596 (M+H+).

Workup

  1. customTo an oven-dried 5 mL conical vial equipped with a magnetic stir bar and under a nitrogen gas atmosphere
  2. customthe reaction was quenched with 5% citric acid (1 mL)
  3. additionthe reaction mixture was diluted with ethyl acetate (15 mL) and water (4 mL)
  4. extractionThe aqueous layer was extracted with ethyl acetate (3×3 mL)
  5. washthe combined organic phases were washed with saturated sodium bicarbonate (3×5 mL), brine (5 mL)
  6. dry with materialdried (NaSO4)
  7. concentrationconcentrated in-vacuo
  8. customPurification by Combiflash (0 to 15% methanol in methylene chloride over 30 min)

Sources & evidence

ORD record
ord-d0dc1d438881419caf5e6cdc1415853f
Source dataset
uspto-grants-2011_07
Patent number
US07973041B2

Reaction notes

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