Cyclopropanecarboxaldehyde → HCID 51354737, compound

HRID 1874629Notes

Reaction equation

HRID 1874629 reaction equation
[NH2:1][CH2:2][C@H:3]([NH:17][C:18](=[O:27])[C@H:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH3:20])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][CH:12]([CH3:16])[CH2:13][CH2:14][CH3:15])=[CH:6][CH:5]=1.[CH:28]1([CH:31]=O)[CH2:30][CH2:29]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>C(#N)C>[CH:28]1([CH2:31][NH:1][CH2:2][C@H:3]([NH:17][C:18](=[O:27])[C@H:19]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH3:20])[C:4]2[CH:5]=[CH:6][C:7]([O:10][CH2:11][CH:12]([CH3:16])[CH2:13][CH2:14][CH3:15])=[CH:8][CH:9]=2)[CH2:30][CH2:29]1

Participants

6

Reactant 4

HCID 123114CyclopropanecarboxaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 58466401HCID 58466401, compound

Product 1

HCID 51354737HCID 51354737, compoundYield 43.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of (2S)-N-((1R)-2-amino-1-(4-(2-methylpentyloxy)phenyl)ethyl)-2-phenylpropanamide (50 mg, 0.136 mmol), prepared according to the procedure described in example 5, in acetonitrile (3 mL), was added cyclopropanecarboxaldehyde (10.23 μL, 0.136 mmol) and stirring was continued for 15 min. To this mixture, sodium triacetoxyborohydride (57.5 mg, 0.271 mmol) was added and the reaction mixture was stirred at room temperature for 1 h. The reaction mixture was transferred to a separatory funnel containing saturated aqueous NaHCO3 solution (10 mL). The aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic layers washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by reverse phase HPLC (acetonitrile/water with 0.1% TFA). The organic solvent was removed on the rotovapor and the aqueous mixture was frozen and placed on the lyophilizer. The product was transferred to a separatory funnel containing saturated aqueous NaHCO3 solution (10 mL). The aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic layers were dried over MgSO4, filtered and concentrated to afford (2S)-N-((1R)-2-(cyclopropylmethylamino)-1-(4-(2-methylpentyloxy)phenyl)ethyl)-2-phenylpropanamide (25 mg, 43.6% yield) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.20-7.36 (m, 5H), 6.92 (d, J=8.6 Hz, 2H), 6.73 (d, J=8.6 Hz, 2H), 6.50 (d, J=6.8 Hz, 1H), 4.99 (q, J=6.3 Hz, 1H), 3.74 (dd, J=8.8, 5.8 Hz, 1H), 3.59-3.68 (m, 2H), 2.95 (dd, J=12.2, 6.4 Hz, 1H), 2.82 (dd, J=12.2, 4.9 Hz, 1H), 2.33-2.47 (m, 2H), 2.08-2.31 (m, 1H), 1.83-1.95 (m, 1H), 1.49 (d, J=7.1 Hz, 3H), 1.26-1.48 (m, 3H), 1.13-1.25 (m, 1H), 0.97 (d, J=6.8 Hz, 3H), 0.90 (t, J=7.1 Hz, 3H), 0.75-0.84 (m, 1H), 0.37-0.46 (m, 2H), −0.02-0.08 (m, 2H); LRMS (ESI) m/e 423.4 [(M+H)+, calcd for C27H39N2O2 423.3].

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 1 h
  2. customThe reaction mixture was transferred to a separatory funnel
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×20 mL)
  4. washThe combined organic layers washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by reverse phase HPLC (acetonitrile/water with 0.1% TFA)
  9. customThe organic solvent was removed on the rotovapor
  10. temperaturethe aqueous mixture was frozen
  11. customThe product was transferred to a separatory funnel
  12. additioncontaining saturated aqueous NaHCO3 solution (10 mL)
  13. extractionThe aqueous layer was extracted with ethyl acetate (2×20 mL)
  14. dry with materialThe combined organic layers were dried over MgSO4
  15. filtrationfiltered
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-d319e54243ea44f9b7163fbfee235018
Source dataset
uspto-grants-2012_11
Patent number
US08304577B2

Reaction notes

Loading…