2-Chloropyridine → HCID 58580251, compound

HRID 1044399Notes

Reaction equation

[OH:1][C:2]([CH3:23])([CH3:22])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH:16]=[CH:15][C:14]([CH2:17][OH:18])=[CH:13][C:12]2=[O:19])=[CH:7][C:6]=1[O:20][CH3:21].Cl[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=1.C(P(C(C)(C)C)C1C=CC2C(=CC=CC=2)C=1C1C2C(=CC=CC=2)C=CC=1)(C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[OH:1][C:2]([CH3:23])([CH3:22])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH:16]=[CH:15][C:14]([CH2:17][O:18][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=3)=[CH:13][C:12]2=[O:19])=[CH:7][C:6]=1[O:20][CH3:21]

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of 1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-4-(hydroxymethyl)pyridin-2(1H)-one Part B (50 mg, 0.16 mmol) and 2-chloropyridine (0.059 mL, 0.63 mmol) in DMF (0.6 mL) was added to a mixture of Pd(OAc)2 (7.0 mg, 0.03 mmol), racemic-2-(di-t-butylphosphino)-1,1′-binaphthyl (19 mg, 0.05 mmol), and Cs2CO3 (128 mg, 0.39 mmol) in 0.4 ml DMF. The mixture was stirred 15 min prior to heating at 80° C. for 6 h. After cooling to RT, the mixture was diluted with EtOAc and was filtered. The filtrate was concentrated and the residue was purified by Prep-HPLC (MeOH/H2O/TFA) to afford the title compound A-4 as a white solid (24 mg, 37% yield). LC-MS, [M+H]+=397. 1H NMR (CDCl3, 400 MHz) δ 8.16 (m, 1H), 7.62 (m, 1H), 7.31 (d, J=7.1 Hz, 1H), 6.91 (m, 5H), 6.72 (s, 1H), 6.28 (dd, J=7.1 and 2.2 Hz, 1H), 5.29 (s, 2H), 3.85 (s, 5H), 1.33 (s, 6H), HPLC-Method 6; 3.07 min.

Workup

temperatureAfter cooling to RT
filtrationwas filtered
concentrationThe filtrate was concentrated
customthe residue was purified by Prep-HPLC (MeOH/H2O/TFA)

Sources & evidence

ORD record: ord-38db6c7df99f46d686960f011212a018
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08563583B2

Reaction notes

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