Dicyclohexylcarbodiimide → HCID 71243493, compound

HRID 1774465Notes

Reaction equation

HRID 1774465 reaction equation
[OH:1][C@@H:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][C@@:3]1([CH2:20][C:21]1[CH:31]=[CH:30][C:24]([C:25]([N:27]([CH3:29])[CH3:28])=[O:26])=[CH:23][CH:22]=1)[C:11]1[CH2:12][C:13]2[C:18]([CH:19]=1)=[CH:17][CH:16]=[CH:15][CH:14]=2.C1CCC(N=C=NC2CCCCC2)CC1.C([NH:64][C@H:65]([C:70](O)=[O:71])[CH2:66][CH:67]([CH3:69])[CH3:68])(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O>CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[NH2:64][C@H:65]([C:70]([O:1][C@@H:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][C@@:3]1([CH2:20][C:21]1[CH:31]=[CH:30][C:24]([C:25](=[O:26])[N:27]([CH3:28])[CH3:29])=[CH:23][CH:22]=1)[C:11]1[CH2:12][C:13]2[C:18]([CH:19]=1)=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:71])[CH2:66][CH:67]([CH3:69])[CH3:68]

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 1549133Fmoc-leucineHCID 71243530HCID 71243530, compound

Product 1

HCID 71243493HCID 71243493, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-{[(1′S,2′S)-1′-hydroxy-1′,3′-dihydro-1H,2′H-2,2′-biinden-2′-yl]methyl}-N,N-dimethylbenzamide (23, 100 mg, 0.24 mmol), DCC (56 mg, 0.28 mmol) and DMAP (3 mg, 0.024 mmol) in ethyl acetate (5 mL), was added Fmoc leucine (84 mg, 0.24 mmol) and then stirred at room temperature for 12 h. The solids were filtered, washed with ethyl acetate (25 ml) and the combined filtrate was washed with 1.5 N HCl (25 mL), water (25 mL), brine (10 mL), dried over anhydrous Na2SO4. The organic layer was evaporated under reduced pressure and the residue 1 (140 mg) was dissolved in dry THF (5 mL) and cooled to 0° C. Dimethylamine (5 mL, 20% in THF) was added drop wise and the reaction mixture was slowly allowed to stir at room temperature for 1 h. The reaction mixture was evaporated under reduced pressure and the residue was purified by CombiFlash using 10% methanol in chloroform as an eluent to yield 45 mg (36%) of the title compound as an off white solid.

Workup

  1. filtrationThe solids were filtered
  2. washwashed with ethyl acetate (25 ml)
  3. washthe combined filtrate was washed with 1.5 N HCl (25 mL), water (25 mL), brine (10 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. customThe organic layer was evaporated under reduced pressure
  6. dissolutionthe residue 1 (140 mg) was dissolved in dry THF (5 mL)
  7. temperaturecooled to 0° C
  8. additionDimethylamine (5 mL, 20% in THF) was added drop wise
  9. stirringto stir at room temperature for 1 h
  10. customThe reaction mixture was evaporated under reduced pressure
  11. customthe residue was purified by CombiFlash

Sources & evidence

ORD record
ord-b6b25bc4e301475fa1f580debea1608f
Source dataset
uspto-grants-2016_02
Patent number
US09260376B2

Reaction notes

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