2-Aminopyridine → 5-[3-(2-Chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-2-(methyloxy)-benzonitrile

HRID 419306Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][C:9]([C:11]2[CH:12]=[CH:13][C:14]([O:19][CH3:20])=[C:15]([CH:18]=2)[C:16]#[N:17])=O)[CH:5]=[CH:4][N:3]=1.Cl[C:22]1[N:27]=[C:26](/[CH:28]=[C:29](/[C:31]2C=CC(OC)=C(C=2)C#N)\O)C=C[N:23]=1.C1C(=O)N(Br)C(=O)C1.NC1C=CC=CN=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[N:27]3[CH:26]=[CH:28][CH:29]=[CH:31][C:22]3=[N:23][C:9]=2[C:11]2[CH:12]=[CH:13][C:14]([O:19][CH3:20])=[C:15]([CH:18]=2)[C:16]#[N:17])[CH:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 65 °C

Procedure

To a tautomeric mixture of 5-[(2-chloro-4-pyrimidinyl)acetyl]-2-(methyloxy)benzonitrile and 5-[(Z)-2-(2-chloro-4-pyrimidinyl)-1-hydroxyethenyl]-2-(methyloxy)benzonitrile (2.87 g, 10.0 mmol) in DCM (250 mL) was added NBS (1.78 g, 10.0 mmol) in one portion. Upon completion by TLC, the reaction was concentrated. The residue was taken up in dioxane (100 mL) and 2-aminopyridine (2.89 g, 30.7 mmol) was added. The reaction was stirred at 65° C. overnight. The reaction was poured into half saturated NaHCO3, extracted with DCM and EtOAc, dried (MgSO4), concentrated and triturated with diethyl ether to provide the title compound (2.36 g, 6.50 mmol, 65%). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.96 (s, 3H), 7.18-7.25 (m, 2H), 7.33 (d, J=9.0 Hz, 1H), 7.52-7.58 (m, 1H), 7.77 (d, J=9.0 Hz, 1H), 7.92 (dd, J=8.8, 2.4 Hz, 1H), 8.00 (d, J=2.2 Hz, 1H), 8.56 (d, J=5.5 Hz, 1H), 9.34-9.39 (m, 1H).

Workup

concentrationUpon completion by TLC, the reaction was concentrated
extractionextracted with DCM and EtOAc
dry with materialdried (MgSO4)
concentrationconcentrated
customtriturated with diethyl ether

Sources & evidence

ORD record: ord-e6278c44c88347c3a67109938e2b9762
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093239B2

Reaction notes

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