2,4-Dichloropyrimidine → 5-(2-chloropyrimidin-4-yloxy)-4-fluoro-2-methyl-1H-indole

HRID 45123Notes

Reaction equation

C1CCN2C(=NCCC2)CC1.[F:12][C:13]1[C:21]([OH:22])=[CH:20][CH:19]=[C:18]2[C:14]=1[CH:15]=[C:16]([CH3:23])[NH:17]2.[Cl:24][C:25]1[N:30]=[C:29](Cl)[CH:28]=[CH:27][N:26]=1>CC#N>[Cl:24][C:25]1[N:30]=[C:29]([O:22][C:21]2[C:13]([F:12])=[C:14]3[C:18](=[CH:19][CH:20]=2)[NH:17][C:16]([CH3:23])=[CH:15]3)[CH:28]=[CH:27][N:26]=1

Participants

Conditions

Temperature: 23 °C

Procedure

DBU (5.48 mL, 36.3 mmol) is added dropwise to a suspension of 4-fluoro-2-methyl-1H-indol-5-ol (5.00 g, 30.3 mmol) and 2,4-dichloropyrimidine (4.60 g, 30.9 mmol) in CH3CN (60 mL) at 0° C. The resulting mixture is warmed to and stirred at 23° C. for 15 h. The reaction mixture is concentrated and the residue is partitioned between 1:1 EtOAc—CH2Cl2 (300 mL) and water (150 mL). The aqueous layer is extracted with EtOAc (2×100 mL). The combined organic layers are washed with brine (100 mL), dried (Na2SO4), and concentrated. The residue is purified by silica gel chromatography (0-100% EtOAc/heptane) to provide 5-(2-chloropyrimidin-4-yloxy)-4-fluoro-2-methyl-1H-indole.

Workup

temperatureThe resulting mixture is warmed to and
concentrationThe reaction mixture is concentrated
customthe residue is partitioned between 1:1 EtOAc—CH2Cl2 (300 mL) and water (150 mL)
extractionThe aqueous layer is extracted with EtOAc (2×100 mL)
washThe combined organic layers are washed with brine (100 mL)
dry with materialdried (Na2SO4)
concentrationconcentrated
customThe residue is purified by silica gel chromatography (0-100% EtOAc/heptane)

Sources & evidence

ORD record: ord-79f28aee0a6f45bcba5eb2c18b2a2252
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08541432B2

Reaction notes

Loading…