Acetic Acid → 2-[1-(diphenylmethyl)azetidin-3-yl]octahydro-6H-pyrido[1,2-a]pyrazin-6-one

HRID 2063306Notes

Reaction equation

HRID 2063306 reaction equation
[C:1]1([CH:7]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:8]2[CH2:11][C:10](=O)[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[CH2:20]1[NH:25][CH2:24][CH2:23][N:22]2[C:26](=[O:30])[CH2:27][CH2:28][CH2:29][CH:21]12.C(O)(=O)C.C([BH3-])#N.C[NH+](C)C>CO>[C:1]1([CH:7]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:8]2[CH2:11][CH:10]([N:25]3[CH2:24][CH2:23][N:22]4[C:26](=[O:30])[CH2:27][CH2:28][CH2:29][CH:21]4[CH2:20]3)[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 37355581-(Diphenylmethyl)azetidin-3-oneHCID 68775865Hexahydro-1H-pyrido[1,2-a]pyrazin-6(2H)-one hydrochlorideHCID 131727185Trimethylammonium cyanoborohydride

Product 1

HCID 161232942-[1-(diphenylmethyl)azetidin-3-yl]octahydro-6H-pyrido[1,2-a]pyrazin-6-oneYield 28%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 1-(diphenylmethyl)azetidin-3-one (see Bioorg. Med. Chem. Lett.; 13; 2003; 2191-2194, 1.32 g, 5.6 mmol) and octahydro-6H-pyrido[1,2-a]pyrazin-6-one hydrochloride (see Bioorg. Med. Chem.; 2004; 71-86; 1.30 g, 6.8 mmol), in methanol (10 mL) was added acetic acid (1 mL). The solution was mixed with (polystyrylmethyl) trimethylammonium cyanoborohydride (4.2 mmol/g, 1.67 g, 8.8 mmol) and the mixture was heated for 5 min at 120° C. using microwave single node heating. The resin was filtered off and then the solvent was removed by evaporation. The product was purified by means of silica gel chromatography using a mixture of ammonia saturated methanol (2%) and methylene chloride. There was obtained 0.58 g (28%) of 2-[1-(diphenylmethyl)azetidin-3-yl]octahydro-6H-pyrido[1,2-a]pyrazin-6-one as an oil. 1H NMR (500 MHz, CDCl3): 1.4 (q, 1H), 1.7 (t, 2H), 1.8-2.0 (m, 3H), 2.3-2.4 (m, 1H), 2.4-2.5 (d, 1H), 2.7-2.8 (t, 3H), 3.0 (m, 3H), 3.4-3.6 (m, 3H), 4.5 (s, 1H), 4.6 (d, 1H), 7.2 (m, 2H), 7.3 (m, 4H), 7.4 (m, 4H); LCMS: m/z 376 (M+1)+.

Workup

  1. temperatureheating
  2. filtrationThe resin was filtered off
  3. customthe solvent was removed by evaporation
  4. customThe product was purified by means of silica gel chromatography
  5. additiona mixture of ammonia saturated methanol (2%) and methylene chloride

Sources & evidence

ORD record
ord-b2bdb8e445fb475faf5822d362c13888
Source dataset
uspto-grants-2012_10
Patent number
US08288370B2

Reaction notes

Loading…