2-Oxopropiononitrile → HCID 66571128, compound

HRID 534174Notes

Reaction equation

HRID 534174 reaction equation
FC(F)(F)C([N:5]([C@@H:13]1[CH2:15][C@H:14]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:6][CH:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1)=O.[CH:24]([C:26]1[CH:31]=[CH:30][C:29]([NH:32][C:33](=[O:35])[CH3:34])=[CH:28][CH:27]=1)=O.[B-]C#N.[Na+].C(C#N)(C)=O.Cl.O1CCOCC1>CO.C(#N)C.C(O)=O.O>[C:16]1([C@@H:14]2[CH2:15][C@H:13]2[NH:5][CH2:6][CH:7]2[CH2:8][CH2:9][N:10]([CH2:24][C:26]3[CH:27]=[CH:28][C:29]([NH:32][C:33](=[O:35])[CH3:34])=[CH:30][CH:31]=3)[CH2:11][CH2:12]2)[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

10

Reactant 5

HCID 694302-OxopropiononitrileHCID 739424-AcetamidobenzaldehydeHCID 204431481,4-Dioxane hydrochlorideHCID 20587905Sodium cyanoborohydride [MI]HCID 867082342,2,2-trifluoro-N-((1R,2S)-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide

Product 1

HCID 66571128HCID 66571128, compoundYield 19.3%

Reagents, catalysts & solvents 4

HCID 284Formic AcidSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 2,2,2-trifluoro-N-(trans-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide (100 mg, 0.306 mmol) in methanol (2 mL) was added N-(4-formylphenyl)acetamide (50.0 mg, 0.306 mmol). The reaction mixture was refluxed for 2 minutes, then cooled down to room temperature. Sodium cyanotrihydroborate (38.5 mg, 0.613 mmol) was added. The reaction mixture was stirred for 1 hour at room temperature. The reaction mixture was injected on preperatory HPLC (5 to 40% AcCN: H2O with 0.1% formic acid modifier). The fractions were collected and evaporated. The resulting oil was dissolved in 6 ml of EtOH and 3 ml of 1 M NaOH. The reaction mixture was stirred for 20 min, and then it was concentrated. The solution was then partitioned between 2 ml of water and 5 mL of EtOAc. Organic layer was separated and evaporated. Resulting oil was dissolved in 3 mL of acetonitrile. 0.5 mL of 4 M HCl/dioxane was added. The reaction mixture was evaporated until dryness. N-(4-((4-(((trans-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)methyl)phenyl)acetamide (28 mg, 0.059 mmol, 19.27% yield) was isolated as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 10.61 (br. s., 1H), 10.20 (s, 1H), 9.60 (br. s., 2H), 7.66 (d, J=8.59 Hz, 2H), 7.48-7.56 (m, 2H), 7.27-7.34 (m, 2H), 7.14-7.26 (m, 3H), 4.10-4.33 (m, 2H), 3.15-3.37 (m, 2H), 2.76-3.14 (m, 5H), 2.59 (ddd, J=3.54, 6.38, 10.04 Hz, 1H), 1.84-2.12 (m, 6H), 1.48-1.68 (m, 3H), 1.17-1.32 (m, 1H); LC-MS Rt=0.53 min; MS (ESI): 378.4 [M+H]+.

Workup

  1. temperatureThe reaction mixture was refluxed for 2 minutes
  2. customThe fractions were collected
  3. customevaporated
  4. dissolutionThe resulting oil was dissolved in 6 ml of EtOH
  5. stirringThe reaction mixture was stirred for 20 min
  6. concentrationit was concentrated
  7. customThe solution was then partitioned between 2 ml of water and 5 mL of EtOAc
  8. customOrganic layer was separated
  9. customevaporated
  10. customResulting oil
  11. customThe reaction mixture was evaporated until dryness

Sources & evidence

ORD record
ord-452ed1eb3507486dacdc179d924ead13
Source dataset
uspto-grants-2014_10
Patent number
US08853408B2

Reaction notes

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