Morpholine → HCID 68940175, compound

HRID 2199722Notes

Reaction equation

HRID 2199722 reaction equation
C([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([C:14]=1[CH2:15][CH2:16][CH2:17][O:18][C:19]1[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=[CH:21][CH:20]=1)=[CH:12][CH:11]=[CH:10][C:9]=2[C:29]1[CH:37]=[CH:36][C:32]([C:33](O)=[O:34])=[CH:31][C:30]=1[CH3:38])=[O:5])C.[NH:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1.Cl.C(N=C=NCCCN(C)C)C>ClCCl.CN(C1C=CN=CC=1)C>[CH3:38][C:30]1[CH:31]=[C:32]([C:33]([N:39]2[CH2:44][CH2:43][O:42][CH2:41][CH2:40]2)=[O:34])[CH:36]=[CH:37][C:29]=1[C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:8]=1[NH:7][C:6]([C:4]([OH:5])=[O:3])=[C:14]2[CH2:15][CH2:16][CH2:17][O:18][C:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][CH:20]=1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 25144469HCID 25144469, compound

Product 1

HCID 68940175HCID 68940175, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of EXAMPLE 98D (75 mg) and morpholine (32 mg) in dichloromethane (2 mL) was added 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide hydrochloride (58 mg) and DMAP (38 mg). The mixture was stirred at room temperature overnight and concentrated. The concentrate was diluted with ethyl acetate (150 mL), washed with 5% HCl, water and brine and dried (Na2SO4), filtered and concentrated. The concentrate was dissolved in THF (4 mL), methanol (2 mL) and water (2 mL). LiOH.H2O (100 mg) was added to the mixture and the mixture was stirred overnight. The mixture was concentrated, the concentrate was acidified with 5% HCl and extracted with ethyl acetate. The extract was washed with brine and dried (Na2SO4), filtered and concentrated. The concentrate was purified by reverse phase HPLC (C-18, 30 to 100% acetonitrile/water/0.1% TFA). 1H NMR (300 MHz, DMSO-d6) δ 12.95 (m, 1H), 10.79 (s, 1H), 8.25 (m, 1H), 7.87 (m, 1H), 7.71 (d, 1H), 7.35-7.57 (m, 6H), 7.27 (s, 1H), 7.08 (m, 2H), 6.90 (d, 1H), 4.21 (t, 1H), 3.64 (m, 8H), 3.37 (t, 2H), 2.26 (t, 2H), 2.07 (s, 3H).

Workup

  1. concentrationconcentrated
  2. additionThe concentrate was diluted with ethyl acetate (150 mL)
  3. washwashed with 5% HCl, water and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe concentrate was dissolved in THF (4 mL)
  8. additionLiOH.H2O (100 mg) was added to the mixture
  9. stirringthe mixture was stirred overnight
  10. concentrationThe mixture was concentrated
  11. extractionextracted with ethyl acetate
  12. washThe extract was washed with brine
  13. dry with materialdried (Na2SO4)
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customThe concentrate was purified by reverse phase HPLC (C-18, 30 to 100% acetonitrile/water/0.1% TFA)

Sources & evidence

ORD record
ord-d0866ead30fe431a95c51868528a5d13
Source dataset
uspto-grants-2016_06
Patent number
US09359296B2

Reaction notes

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