4-(Bromomethyl)phenylacetic acid → HCID 77844320, compound

HRID 1519161Notes

Reaction equation

[CH:1]1([C:5]2[C:10]([OH:11])=[C:9]([F:12])[C:8]([C:13]3[CH:22]=[N:21][C:20]4[NH:19][CH2:18][CH2:17][O:16][C:15]=4[CH:14]=3)=[CH:7][CH:6]=2)[CH2:4][CH2:3][CH2:2]1.Br[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([CH2:31][C:32]([OH:34])=[O:33])=[CH:27][CH:26]=1.CC(C)([O-])C.[K+]>CS(C)=O>[CH:1]1([C:5]2[C:10]([O:11][CH2:24][C:25]3[CH:26]=[CH:27][C:28]([CH2:31][C:32]([OH:34])=[O:33])=[CH:29][CH:30]=3)=[C:9]([F:12])[C:8]([C:13]3[CH:22]=[N:21][C:20]4[NH:19][CH2:18][CH2:17][O:16][C:15]=4[CH:14]=3)=[CH:7][CH:6]=2)[CH2:2][CH2:3][CH2:4]1

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of 6-cyclobutyl-3-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-2-fluorophenol (50 mg, 0.17 mmol) and 2-(4-(bromomethyl)phenyl)acetic acid (38 mg, 0.17 mmol) in DMSO (1 mL) was treated with potassium tert-butoxide (38 mg, 0.33 mmol) and stirred for 16 hours at 80° Celsius. The reaction was then cooled to rt, filtered, and the filtrate subjected directly to HPLC purification to give (4-{[6-cyclobutyl-3-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-2-fluorophenoxy]methyl}phenyl)acetic acid (8 mg, 9%). MS (ESI): mass calcd. for C26H25FN2O4, 448.18; m/z found, 449.2 [M+H]+. 1H NMR (600 MHz, CD3OD) δ 7.72 (s, 1H), 7.60 (s, 1H), 7.40 (d, J=8.1, 2H), 7.31 (d, J=8.1, 2H), 7.19 (d, J=6.0, 2H), 5.04 (s, 2H), 4.38-4.32 (m, 2H), 3.78-3.72 (m, 1H), 3.71-3.67 (m, 2H), 3.63 (s, 2H), 2.29-2.22 (m, 2H), 2.16-2.07 (m, 2H), 2.04-1.97 (m, 1H), 1.84 (t, J=9.6, 1H).

Workup

temperatureThe reaction was then cooled to rt
filtrationfiltered
customthe filtrate subjected directly to HPLC purification

Sources & evidence

ORD record: ord-3ce1549ca06d4f58b4354470a7ce1915
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09073876B2

Reaction notes

Loading…