Ethyl Acetate → Benzyl 4-(8-chloroimidazo[1,5-a]pyrazin-3-yl)piperidine-1-carboxylate

HRID 2076506Notes

Reaction equation

HRID 2076506 reaction equation
[Cl:1][C:2]1[C:3]([CH2:8][NH:9][C:10]([C:12]2(C(OCC3C=CC=CC=3)=O)[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=O)=[N:4][CH:5]=[CH:6][N:7]=1.O=P(Cl)(Cl)Cl.C([O-])(O)=O.[Na+].[CH3:38][CH2:39][O:40][C:41](C)=[O:42]>CN(C=O)C.O>[Cl:1][C:2]1[C:3]2[N:4]([C:10]([CH:12]3[CH2:13][CH2:14][N:15]([C:41]([O:40][CH2:39][C:38]4[CH:16]=[CH:17][CH:12]=[CH:13][CH:14]=4)=[O:42])[CH2:16][CH2:17]3)=[N:9][CH:8]=2)[CH:5]=[CH:6][N:7]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 86631919HCID 86631919, compound

Product 1

HCID 42609367Benzyl 4-(8-chloroimidazo[1,5-a]pyrazin-3-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a suspension of benzyl 4-{[(3-chloropyrazin-2-yl)methyl]carbamoyl}piperidine-4-carboxylate (0.100 g, 0.220 mmol) in EtOAc (0.9 mL) and DMF (0.068 mL) at 0° C. was slowly added POCl3 (0.082 mL, 0.88 mmol). After stirring at rt for an hour the mixture was cooled to 0° C. then treated with solid NaHCO3. The mixture was stirred for 20 min at rt, diluted with water and extracted with EtOAc (3×20 mL). The combined extracts were washed with water (2×30 mL) and brine (30 mL), then dried over Na2SO4, and concentrated in vacuo to yield 2.07 g of desired product. 1H NMR (400 MHz, CDCl3): δ 1.98-2.04 (m, 4H), 3.03-3.20 (m, 3H), 4.30-4.33 (m, 2H), 5.16 (s, 2H), 7.33 (d, J=5.2 Hz, 1H), 7.35-7.38 (m, 5H), 7.26 (d, J=4.4 Hz, 1H), 7.79 (s, 1H). MS (ES+): m/z 371.22 [MH+].

Workup

  1. temperaturewas cooled to 0° C.
  2. stirringThe mixture was stirred for 20 min at rt
  3. extractionextracted with EtOAc (3×20 mL)
  4. washThe combined extracts were washed with water (2×30 mL) and brine (30 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-33401328b54243c5a4fadf75cdb00b21
Source dataset
uspto-grants-2011_04
Patent number
US07923555B2

Reaction notes

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