Pyridine → HCID 58547120, compound

HRID 1850325Notes

Reaction equation

HRID 1850325 reaction equation
[N:1]1([C:8]2[C:9]([CH:14]3[CH2:17][N:16]([C:18]4[CH:27]=[CH:26][C:25]5[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=5)[N:19]=4)[CH2:15]3)=[N:10][CH:11]=[CH:12][N:13]=2)[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.N1C=CC=CC=1.N1(C2C=CN=CC=2)CCCC1.[C:45](Cl)(=[O:48])[O:46][CH3:47]>C(Cl)Cl>[N:19]1[C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:26]=[CH:27][C:18]=1[N:16]1[CH2:15][CH:14]([C:9]2[C:8]([N:1]3[CH2:7][CH2:6][CH2:5][N:4]([C:45]([O:46][CH3:47])=[O:48])[CH2:3][CH2:2]3)=[N:13][CH:12]=[CH:11][N:10]=2)[CH2:17]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 6586Methyl chloroformateHCID 755674-PyrrolidinopyridineHCID 54675515HCID 54675515, compound

Product 1

HCID 58547120HCID 58547120, compoundYield 70.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a round bottomed flask was added 2-(3-(3-(1,4-diazepan-1-yl)pyrazin-2-yl)azetidin-1-yl)quinoline (0.0772 g, 0.214 mmol), pyridine (commercially available through Aldrich, 0.035 ml, 0.428 mmol), and 4-(pyrrolidin-1-yl)pyridine (commercially available through Alfa Aesar, 0.032 g, 0.214 mmol) and the reaction was allowed to stir at RT in DCM (0.714 ml). Methyl carbonochloridate (commercially available through Aldrich, 0.021 ml, 0.321 mmol) was added and allowed to stir overnight. Upon completion, the solvent was evaporated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage 50 g SNAP HP-silica column, eluting with a gradient of 0.5% to 5% MeOH in CH2CL2, to provide methyl 4-(3-(1-(quinolin-2-yl)azetidin-3-yl)pyrazin-2-yl)-1,4-diazepane-1-carboxylate (0.0632 g, 0.151 mmol, 70.5% yield). ESI-MS (M+1): 419.0. PDE10 IC50 (μM): 0.0046.

Workup

  1. customUpon completion, the solvent was evaporated
  2. customchromatographed through a Biotage 50 g SNAP HP-silica column
  3. washeluting with a gradient of 0.5% to 5% MeOH in CH2CL2

Sources & evidence

ORD record
ord-ba1af15b7a3b4e0aa678aac0f649de8f
Source dataset
uspto-grants-2015_02
Patent number
US08957073B2

Reaction notes

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