Hydrochloric Acid → HCID 58651188, compound

HRID 1830596Notes

Reaction equation

HRID 1830596 reaction equation
[NH2:1][C@H:2]([CH2:19][C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1)[C:3]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[O:17][CH3:18])[CH2:7][CH2:6]1)=O.B.C1COCC1.Cl>C1COCC1>[CH3:18][O:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[N:8]1[CH2:9][CH2:10][N:5]([CH2:3][C@H:2]([NH2:1])[CH2:19][C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)[CH2:6][CH2:7]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 2723981Borane;tetrahydrofuranHCID 58651191HCID 58651191, compound

Product 1

HCID 58651188HCID 58651188, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2R)-2-Amino-1-[4-(2-methoxy-phenyl)-piperazin-1-yl]-3-pyridin-3-yl-propan-1-one (6.23 g; 18.3 mmol, from Example 2) in THF (60 mL) was added, dropwise, BH3.THF (1.0M/THF) (73 mL; 73 mmol). The mixture was stirred at reflux for 2.5 hours, then allowed to stir at ambient temperature overnight. The mixture was cooled to 0–5° C., cautiously treated with 5M HCl (30 mL), stirred at ambient temperature for 4 hours. The mixture was then concentrated on a rotary evaporator to remove THF, diluted with water (30 mL), and the pH adjusted to 10 with concentrated ammonium hydroxide. The product was extracted into ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, and the solvent removed in vacuo to yield the title compound as a free base (5.24 g.; 88%). The analytical sample was converted to the hydrochloride salt with ethereal HCl to yield a white crystalline solid, m.p. 168–169° C.; MS (+) ESI, [M+H]+ @ m/z 327; 1H NMR, 400 MHz, DMSO-d6. Analysis for C19H26N4O.HCl.H2O.0.25 C2H6O Calculated: C, 62.21; H, 8.16; N, 14.88 Found: C, 61.72; H, 7.65; N, 14.17.

Workup

  1. temperatureat reflux for 2.5 hours
  2. stirringto stir at ambient temperature overnight
  3. temperatureThe mixture was cooled to 0–5° C.
  4. stirringstirred at ambient temperature for 4 hours
  5. concentrationThe mixture was then concentrated on a rotary evaporator
  6. customto remove THF
  7. additiondiluted with water (30 mL)
  8. extractionThe product was extracted into ethyl acetate (3×50 mL)
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-2722bda385e04d75933345209316cc54
Source dataset
uspto-grants-2006_06
Patent number
US07067518B2

Reaction notes

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