1,2-Dichloroethane → n-{1-[(Benzyl-methyl-amino)-methyl]-1-cyano-3-phenyl-propyl}-2-cyclohexylmethyl-4-morpholin-4-yl-oxo-butyramide

HRID 480246Notes

Reaction equation

HRID 480246 reaction equation
[CH:1]1([CH2:7][CH:8]([C:12](=[O:20])[CH2:13][N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:9]([OH:11])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)CCl.[NH2:25][C:26]([CH2:37][N:38]([CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[CH3:39])([CH2:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:27]#[N:28].CN1CCOCC1>C(Cl)Cl>[CH2:40]([N:38]([CH2:37][C:26]([NH:25][C:9](=[O:11])[CH:8]([CH2:7][CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1)[C:12](=[O:20])[CH2:13][N:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1)([C:27]#[N:28])[CH2:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH3:39])[C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 18768971HCID 18768971, compoundHCID 187689872-Cyclohexylmethyl-4-morpholin-4-yl-oxo-butanoic acid

Product 1

HCID 18768945n-{1-[(Benzyl-methyl-amino)-methyl]-1-cyano-3-phenyl-propyl}-2-cyclohexylmethyl-4-morpholin-4-yl-oxo-butyramideYield 25%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2-Cyclohexylmethyl-4-morpholin-4-yl-oxo-butanoic acid (0.097 g, 0.34 mmol, 1.0 equiv) was dissolved in 10 mL of CH2Cl2 followed by addition of EDC (0.065 g, 0.34 mmol, 1.0 equiv). The solution was stirred for 15 min at which time a solution of 2-amino-2-[(benzyl-methyl-amino)-methyl]-4-phenyl-butyronitrile (0.10 g, 0.34 mmol, 1.0 equiv) in 5 mL of CH2Cl2 was added followed by N-methylmorpholine (0.137 g, 1.36 mmol, 4.0 equiv). The resulting solution was stirred at room temperature for 72 h. The volatiles were removed in vacuo and the residue was redissolved in 100 mL of EtOAc and the solution was washed 2×25 mL brine. The organic layer was evaporated to dryness and the crude product was purified by semi-prep reverse-phase HPLC using 40% CH3CN in water to 90% over a time of 25 min. The appropriate fractions were combined and concentrated to yield the desired product as a thick oil (0.047 g, 25%); MS, m/Z 559=M+1.

Workup

  1. additionwas added
  2. customThe volatiles were removed in vacuo
  3. dissolutionthe residue was redissolved in 100 mL of EtOAc
  4. washthe solution was washed 2×25 mL brine
  5. customThe organic layer was evaporated to dryness
  6. customthe crude product was purified by semi-prep reverse-phase
  7. customover a time of 25 min
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-8aa1c4d129064966a0d66e58bc32b82e
Source dataset
uspto-grants-2003_11
Patent number
US06649642B2

Reaction notes

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