4-Methylmorpholine → HCID 69591139, compound

HRID 989520Notes

Reaction equation

HRID 989520 reaction equation
CN1CCOCC1.Cl[C:9]1[N:14]=[C:13](OC)[N:12]=[C:11](OC)[N:10]=1.[C:19]([O:23][C:24]([NH:26][C:27]([CH3:42])([CH3:41])[C:28]([NH:30][CH:31]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:32]([OH:34])=O)=[O:29])=[O:25])([CH3:22])([CH3:21])[CH3:20].Cl.Cl.NC1N=C([CH:51]([C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[C:52]([N:54]2[CH2:58][CH2:57][CH2:56][CH2:55]2)=[O:53])NC=1>C(Cl)Cl.C1COCC1.CCOC(C)=O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[C:19]([O:23][C:24]([NH:26][C:27]([CH3:41])([CH3:42])[C:28]([NH:30][C@@H:31]([C:32](=[O:34])[NH:10][C:9]1[N:14]=[CH:13][N:12]([CH:51]([C:59]2[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=2)[C:52](=[O:53])[N:54]2[CH2:55][CH2:56][CH2:57][CH2:58]2)[CH:11]=1)[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)=[O:29])=[O:25])([CH3:22])([CH3:20])[CH3:21]

Participants

9

Reactant 4

HCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 22252879HCID 22252879, compoundHCID 178478666HCID 178478666, compound

Product 1

HCID 69591139HCID 69591139, compoundYield 40.7%

Reagents, catalysts & solvents 4

HCID 311Citric AcidSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-methylmorpholine (0.25 mL, 2.27 mmol) was added to a suspension of 2-chloro-4,6-dimethoxy-1,3,5-triazine (405 mg, 2.27 mmol) and 2-{2-[(tert-butoxy)carbonylamino]-2-methylpropanoylamino}-2-phenylacetic acid (570 mg, 1.69 mmol) in CH2Cl2 (7 mL) and THF (2 mL) at 23° C. The mixture stirred for 2 h and 2-(4-aminoimidazolyl)-2-phenyl-1-pyrrolidinylethan-1-one dihydrochloride (779 mg, 2.27 mmol) was added in one portion. After 16 h, the reaction was diluted with EtOAc (50 mL) and 10% (w/w) aqueous citric acid. The phases were separated, and the organic layer was washed with 20 mL each of saturated aqueous NaHCO3 and saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (gradient 2/98 to 6/94 MeOH/CH2Cl2) to give 405 mg (40%) of the title compound. 1H NMR (CDCl3, 300 MHz) d 10.61 (m, 1H), 7.75 (s, 1H), 7.45-7.15 (m, 12H), 5.95 (s, 1H), 5.80 (m, 1H), 3.60-3.38 (m, 3H), 3.10 (m, 1H), 2.15 (m, 1H), 1.98-1.65 (m, 3H), 1.50-1.05 (m, 15H); IR (CHCl3) 3400, 3000,1706, 1661, 1486, 1455, 1157 cm−1; MS (electrospray) m/z 588 (M+H), 589 (M−H), 587.

Workup

  1. waitAfter 16 h
  2. customThe phases were separated
  3. washthe organic layer was washed with 20 mL each of saturated aqueous NaHCO3 and saturated aqueous NaCl
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (gradient 2/98 to 6/94 MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-edab0c09657e4a30a273754ecd3d93d1
Source dataset
uspto-grants-2003_10
Patent number
US06639076B1

Reaction notes

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