2-(Tributylstannyl)-1,3-thiazole → 6-[(4-Fluoro-3-methylphenoxy)methyl]-2-methyl-1-[5-methyl-2-(1,3-thiazol-2-yl)benzoyl]azepane

HRID 467483Notes

Reaction equation

[F:1][C:2]1[CH:27]=[CH:26][C:5]([O:6][CH2:7][CH:8]2[CH2:14][N:13]([C:15](=[O:24])[C:16]3[CH:21]=[C:20]([CH3:22])[CH:19]=[CH:18][C:17]=3I)[CH:12]([CH3:25])[CH2:11][CH2:10][CH2:9]2)=[CH:4][C:3]=1[CH3:28].C([Sn](CCCC)(CCCC)[C:34]1[S:35][CH:36]=[CH:37][N:38]=1)CCC>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:27]=[CH:26][C:5]([O:6][CH2:7][CH:8]2[CH2:14][N:13]([C:15](=[O:24])[C:16]3[CH:21]=[C:20]([CH3:22])[CH:19]=[CH:18][C:17]=3[C:34]3[S:35][CH:36]=[CH:37][N:38]=3)[CH:12]([CH3:25])[CH2:11][CH2:10][CH2:9]2)=[CH:4][C:3]=1[CH3:28]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 6-[(4-fluoro-3-methylphenoxy)methyl]-1-(2-iodo-5-methylbenzoyl)-2-methylazepane (3-1, 50 mg, 0.10 mmol, 1.0 equiv), tetrakis(triphenyl phosphine)palladium (35 mg, 0.030 mmol, 0.30 equiv) and 2-tributylstannylthiazole (94 mg, 0.25 mmol, 2.5 equiv) in toluene (1 mL) was heated at 100° C. for 1 hour. The reaction was cooled and filtered. The filtrate was concentrated and purified by reverse phase liquid chromatography (Sunfire C18 OBD 5 um, 20×150 mm column; 0-100% CH3CN/H2O gradient w/0.10% TFA present) to yield 6-[(4-fluoro-3-methylphenoxy)methyl]-2-methyl-1-[5-methyl-2-(1,3-thiazol-2-yl)benzoyl]azepane (3-2). δ 7.96-6.14 (m, 8H), 4.77-0.88 (m, 21H). LRMS m/z (M+H) 496.2 found, 496.1 required.

Workup

temperatureThe reaction was cooled
filtrationfiltered
concentrationThe filtrate was concentrated
custompurified by reverse phase liquid chromatography (Sunfire C18 OBD 5 um, 20×150 mm column; 0-100% CH3CN/H2O gradient w/0.10% TFA present)

Sources & evidence

ORD record: ord-26e90d9342ec49e5b14b943a1911ee2c
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08623863B2

Reaction notes

Loading…