Dimethylformamide → 4-[8-Chloro-1-(2-phenyl-quinolin-7-yl)-imidazo[1,5-a]pyrazin-3-yl]-piperidine-1-carboxylic acid benzyl ester

HRID 493763Notes

Reaction equation

HRID 493763 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17](=O)[NH:18][CH:19]([C:36]2[C:41]([Cl:42])=[N:40][CH:39]=[CH:38][N:37]=2)[C:20]2[CH:29]=[C:28]3[C:23]([CH:24]=[CH:25][C:26]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[N:27]3)=[CH:22][CH:21]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C=O)C.O=P(Cl)(Cl)Cl>CC#N>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][CH:14]([C:17]2[N:37]3[CH:38]=[CH:39][N:40]=[C:41]([Cl:42])[C:36]3=[C:19]([C:20]3[CH:29]=[C:28]4[C:23]([CH:24]=[CH:25][C:26]([C:30]5[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=5)=[N:27]4)=[CH:22][CH:21]=3)[N:18]=2)[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 576810294-{[(3-Chloro-pyrazin-2-yl)-(2-phenyl-quinolin-7-yl)-methyl]carbamoyl}-piperidine-1-carboxylic acid benzyl ester

Product 1

HCID 536290294-[8-Chloro-1-(2-phenyl-quinolin-7-yl)-imidazo[1,5-a]pyrazin-3-yl]-piperidine-1-carboxylic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
55 °C

Procedure

4-{[(3-Chloro-pyrazin-2-yl)-(2-phenyl-quinolin-7-yl)-methyl]-carbamoyl}-piperidine-1-carboxylic acid benzyl ester (2.1 g, 3.6 mmol) was dissolved in CH3CN (126.0 mL) and DMF (0.4 mL) in a round bottom flask equipped with a condenser. The reaction was charged with POCl3 (1.7 mL, 17.9 mmol) and stirred at 55° C. for 3 h. The reaction mixture was concentrated in vacuo, redissolved in DCM, cooled to 0° C., and charged with 2M NH3 in isopropanol to basic pH. Hydromatrix was added, the mixture was concentrated in vacuo, and the resulting residue was purified by silica gel chromatography (Jones Flashmaster, 20 g/70 mL cartridge, eluting with 100% CH2Cl2 to 2% CH3CN/CH2Cl2) to afford 4-[8-chloro-1-(2-phenyl-quinolin-7-yl)-imidazo[1,5-a]pyrazin-3-yl]-piperidine-1-carboxylic acid benzyl ester as a yellow solid; MS (ES+): m/z 574 (100) [MH+]; HPLC: tR=4.2 min (OpenLynx, polar—5 min).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionredissolved in DCM
  3. temperaturecooled to 0° C.
  4. additioncharged with 2M NH3 in isopropanol to basic pH
  5. additionHydromatrix was added
  6. concentrationthe mixture was concentrated in vacuo
  7. customthe resulting residue was purified by silica gel chromatography (Jones Flashmaster, 20 g/70 mL cartridge, eluting with 100% CH2Cl2 to 2% CH3CN/CH2Cl2)

Sources & evidence

ORD record
ord-4ee08da75e9f43efabb75cf44d4859c7
Source dataset
uspto-grants-2009_05
Patent number
US07534797B2

Reaction notes

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