Sodium Bicarbonate → 2-Chloro-5-((5-(3-chlorophenyl)-6-methoxypyridin-3-yl)methyl)pyrimidine

HRID 578828Notes

Reaction equation

Br[CH2:2][C:3]1[CH:4]=[C:5]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=2)[C:6]([O:9][CH3:10])=[N:7][CH:8]=1.[Cl:18][C:19]1[N:24]=[CH:23][C:22](B(O)O)=[CH:21][N:20]=1.C([O-])(O)=O.[Na+]>C(#N)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[Cl:18][C:19]1[N:24]=[CH:23][C:22]([CH2:2][C:3]2[CH:8]=[N:7][C:6]([O:9][CH3:10])=[C:5]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=3)[CH:4]=2)=[CH:21][N:20]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of 5-(bromomethyl)-3-(3-chlorophenyl)-2-methoxypyridine (Intermediate 2, 100 mg, 0.321 mmol), (2-chloropyrimidin-5-yl)boronic acid (76 mg, 0.481 mmol) in ACN (3.2 mL) was added NaHCO3 (417 mg, 1.282 mmol) and PdCl2(dppf)-DCM (23 mg, 0.032 mmol). The reaction was heated under microwave conditions, at 120° C. for 12 minutes. Water was removed from the reaction with a pipette, and the crude reaction mix was filtered thru CELITE®, and washed with EtOAc. The combined organics were dried (Na2SO4), filtered and concentrated onto silica. Purification (FCC, SiO2, 30-70% EtOAc/hexanes) afforded the title compound (61 mg, 55%). 1H NMR (400 MHz, DMSO-d6) δ 8.34 (s, 2H), 8.11 (d, J=2.0 Hz, 1H), 7.70 (d, J=2.0 Hz, 1H), 7.58 (t, J=1.8 Hz, 1H), 7.53-7.36 (m, 3H), 3.83 (s 2H), 3.73 (s, 3H). [M+H]=346.11.

Workup

customWater was removed from the reaction with a pipette
customthe crude reaction
additionmix
filtrationwas filtered thru CELITE®
washwashed with EtOAc
dry with materialThe combined organics were dried (Na2SO4)
filtrationfiltered
concentrationconcentrated onto silica
customPurification (FCC, SiO2, 30-70% EtOAc/hexanes)

Sources & evidence

ORD record: ord-f9e59550e4a74ae6a361d9e23b8b52c9
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040692B2

Reaction notes

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