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

HRID 1163133
Notes
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Reaction equation

HRID 1163133 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
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

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 6342
Acetonitrile
Solvent

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-c6c004a264a54aac947061a4e03fba02
Source dataset
uspto-grants-2010_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07820662B2

Reaction notes

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