4-Bromo-3,5-dimethylpyridine → 8-(cyclopentyloxy)-4-(3,5-dimethylpyridin-4-ylamino)-7-methoxy-2H-chromen-2-one

HRID 20641Notes

Reaction equation

[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([O:14][CH:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)[C:8]([O:12][CH3:13])=[CH:9][CH:10]=2)[O:5][C:4](=[O:20])[CH:3]=1.Br[C:22]1[C:27]([CH3:28])=[CH:26][N:25]=[CH:24][C:23]=1[CH3:29].CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[CH:15]1([O:14][C:7]2[C:8]([O:12][CH3:13])=[CH:9][CH:10]=[C:11]3[C:6]=2[O:5][C:4](=[O:20])[CH:3]=[C:2]3[NH:1][C:22]2[C:27]([CH3:28])=[CH:26][N:25]=[CH:24][C:23]=2[CH3:29])[CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 4-amino-8-(cyclopentyloxy)-7-methoxy-2H-chromen-2-one (0.176 g, 0.640 mmol, Example 3, Step 1), 4-bromo-3,5-dimethylpyridine (0.108 g, 0.580 mmol), Pd2(dba)3 (55 mg, 0.06 mmol), 2,2-dicyclohexylphosphorane triisopropylbiphenyl (55 mg, 0.12 mmol), sodium tert-butoxide (67 mg, 0.69 mmol), and dry toluene (3 mL) was heated to 110° C. under N2 for 2 h. The mixture was allowed to cool to rt, filtered through Celite, washed with EtOAc, concentrated, and purified by reverse-phase HPLC (20→100% acetonitrile:water) to give 8-(cyclopentyloxy)-4-(3,5-dimethylpyridin-4-ylamino)-7-methoxy-2H-chromen-2-one: 1H NMR (400 MHz, DMSO-d6): δ 9.10 (s, 1H), 8.43 (s, 2H), 7.93 (d, 1H), 7.17 (d, 1H), 4.83 (m, 1H), 4.29 (s, 1H), 3.90 (s, 3H), 2.15 (s, 6H) 1.86-1.53 (m, 8H); MS (ESI): 380.9.

Workup

temperatureto cool to rt
filtrationfiltered through Celite
washwashed with EtOAc
concentrationconcentrated
custompurified by reverse-phase HPLC (20→100% acetonitrile:water)

Sources & evidence

ORD record: ord-c339ec8190ec426683dd7e6371209133
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07745646B2

Reaction notes

Loading…