4-Methylmorpholine → HCID 87349528, compound

HRID 1010480Notes

Reaction equation

HRID 1010480 reaction equation
C([O:8][NH:9][C:10]([C@@H:12]1[C@@H:17]([C:18](=[O:39])[NH:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][C:28]3[C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[N:31]=[C:30]([CH3:38])[CH:29]=3)=[CH:22][CH:21]=2)[CH2:16][CH2:15][CH:14]([CH2:40][C:41](O)=[O:42])[CH2:13]1)=[O:11])C1C=CC=CC=1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[NH:77]1[CH2:82][CH2:81][CH2:80][CH2:79][CH2:78]1.CN1CCOCC1>CN(C=O)C>[OH:8][NH:9][C:10]([C@H:12]1[CH2:13][CH:14]([CH2:40][C:41](=[O:42])[N:77]2[CH2:82][CH2:81][CH2:80][CH2:79][CH2:78]2)[CH2:15][CH2:16][C@@H:17]1[C:18]([NH:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][C:28]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[N:31]=[C:30]([CH3:38])[CH:29]=2)=[CH:22][CH:21]=1)=[O:39])=[O:11]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 8082PiperidineHCID 2724699PyBOPHCID 87348872{3-(s)-Benzyloxycarbamoyl-4-(s)-[4-(2-methyl-quinolin-4-ylmethoxy)-phenylcarbamoyl]-cyclohexyl}-acetic acid

Product 1

HCID 87349528HCID 87349528, compoundYield 110.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Part 10: 4-(2-Oxo-2-piperidin-1-yl-ethyl)-cyclohexan-1-(S)-,2-(S)-dicarboxylic acid 2-(S)-(benzyloxy-amide) 1-(S)-{[4-(2-methyl-quinolin-4-ylmethoxy)-phenyl]-amide. To an oven-dried 5 mL conical vial equipped with a magnetic stir bar and under a nitrogen gas atmosphere was placed sequentially: {3-(S)-benzyloxycarbamoyl-4-(S)-[4-(2-methyl-quinolin-4-ylmethoxy)-phenylcarbamoyl]-cyclohexyl}-acetic acid (20 mg, 0.034 mmol), anhydrous DMF (1 mL), PyBOP reagent (20 mg, 0.038 mmol), piperidine (0.010 mL, 0.101 mmol), and 4-methyl morpholine (0.01 mL, 0.092 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 10% methanol in methylene chloride over 30 min) to afford 21 mg (95%) of the desired amide. LCMS (ESI): 649 (M+1H).

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 10% methanol in methylene chloride over 30 min)

Sources & evidence

ORD record
ord-28fda88ad64245c7af8fbe212119862d
Source dataset
uspto-grants-2011_07
Patent number
US07973041B2

Reaction notes

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