1,2-Dichloroethane → 6-[(4-Fluoro-3-methylphenoxy)methyl]-1-(2-iodo-5-methylbenzoyl)-2-methylazepane

HRID 467482Notes

Reaction equation

[F:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][CH2:7][CH:8]2[CH2:14][NH:13][CH:12]([CH3:15])[CH2:11][CH2:10][CH2:9]2)=[CH:4][C:3]=1[CH3:18].[I:19][C:20]1[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][C:21]=1[C:22](O)=[O:23].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C=O)C>[F:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][CH2:7][CH:8]2[CH2:14][N:13]([C:22](=[O:23])[C:21]3[CH:25]=[C:26]([CH3:29])[CH:27]=[CH:28][C:20]=3[I:19])[CH:12]([CH3:15])[CH2:11][CH2:10][CH2:9]2)=[CH:4][C:3]=1[CH3:18]

Participants

Conditions

Temperature: 23 °C

Procedure

A solution of 6-[(4-fluoro-3-methylphenoxy)methyl]-2-methylazepane (2-7, 120 mg, 0.48 mmol, 1.0 equiv) in DMF (5 mL) was treated with 2-iodo-5-methylbenzoic acid (140 mg, 0.52 mmol, 1.1 equiv), EDC (110 mg, 0.57 mmol, 1.2 equiv), HOBT (88 mg, 0.57 mmol, 1.2 equiv) and triethylamine (0.20 mL, 140 mg, 1.4 mmol, 3.0 equiv) and the resulting mixture was stirred at 23° C. for 16 hours. The mixture was filtered 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]-1-(2-iodo-5-methylbenzoyl)-2-methylazepane (3-1). δ 7.87 (m, 1H), 7.10 (m, 6H), 6.43 (m, 1H), 4.79-1.04 (m, 19H). LRMS m/z (M+H) 496.2 found, 496.1 required.

Workup

filtrationThe mixture was filtered
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-ea08dd56f07a40fca5da74aa8a8fcd4b
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08623863B2

Reaction notes

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