4-Methylmorpholine → HCID 22719739, compound

HRID 1582069Notes

Reaction equation

HRID 1582069 reaction equation
Cl.[CH3:2][N:3](C)[CH2:4][CH2:5][CH2:6][N:7]=C=NCC.O.ON1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2N=N1.CN1CC[O:28]CC1.[CH2:31]([O:38][C:39]([CH:41]([CH2:51][CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)[CH2:42][C:43]1([C:48]([OH:50])=O)[CH2:47][CH2:46][CH2:45][CH2:44]1)=[O:40])C1C=CC=CC=1>CN(C)C=O>[CH3:2][NH:3][C:4](=[O:28])[CH2:5][CH2:6][NH:7][C:48]([C:43]1([CH2:42][CH:41]([CH2:51][CH2:52][C:53]2[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=2)[C:39]([O:38][CH2:31][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:40])[CH2:44][CH2:45][CH2:46][CH2:47]1)=[O:50]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 22719740HCID 22719740, compound

Product 1

HCID 22719739HCID 22719739, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (122 mg, 0.64 mmol), 1-hydroxybenzotriazole hydrate (86 mg, 0.64 mmol) and 4-methylmorpholine (173 μl, 1.59 mmol) were added sequentially to a cooled solution of 1-{2-[(benzyloxy)carbonyl]4-phenylbutyl}cyclopentane-carboxylic acid (EP 274234) (202 mg, 0.53 mmol) in N,N-dimethylformamide (5 ml) at room temperature, followed by the amine hydrochloride from preparation 6 (6/23) (146 mg, 1.06 mmol), and the reaction stirred at 90° C. for 18 hours. The cooled solution was concentrated under reduced pressure and the residue partitioned between water (20 ml) and ethyl acetate (100 ml). The layers were separated, the organic phase washed with water (3×30 ml), brine (25 ml) dried (MgSO4), and evaporated under reduced pressure to give a clear oil. The crude product was purified by column chromatography on silica gel using dichloromethane:methanol (98:2) as eluant to afford the title compound as a colourless oil, 162 mg, 67%; 1H NMR (CDCl3, 400 MHz) δ: 1.38-1.53 (m, 2H), 1.53-1.96 (m, 8H), 2.02 (m, 2H), 2.27 (t, 2H), 2.46 (m, 3H), 2.76 (d, 3H), 3.44 (m, 2H), 5.13 (s, 2H), 5.79 (bs, 1H), 6.38 (m, 1H), 7.06 (d, 2H), 7.18 (m, 1H), 7.22 (m, 2H), 7.38 (m, 5H); LRMS: m/z 465.5 (MH+).

Workup

  1. concentrationThe cooled solution was concentrated under reduced pressure
  2. customthe residue partitioned between water (20 ml) and ethyl acetate (100 ml)
  3. customThe layers were separated
  4. washthe organic phase washed with water (3×30 ml), brine (25 ml)
  5. dry with materialdried (MgSO4)
  6. customevaporated under reduced pressure
  7. customto give a clear oil
  8. customThe crude product was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-3886bc4340a545a88a19d7b9b1ac2ee3
Source dataset
uspto-grants-2004_05
Patent number
US06734186B1

Reaction notes

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