Anisole → N-[(1S,2S)-2-Amino-4,4-difluorocyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide

HRID 1750563Notes

Reaction equation

[F:1][C:2]1([F:29])[CH2:6][C@H:5]([NH:7][C:8](=[O:20])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[N:15]2[N:19]=[CH:18][CH:17]=[N:16]2)[C@@H:4]([NH:21]S(C(C)(C)C)(=O)=O)[CH2:3]1.C1(OC)C=CC=CC=1.FC(F)(F)S(O)(=O)=O>C(Cl)Cl>[NH2:21][C@H:4]1[CH2:3][C:2]([F:29])([F:1])[CH2:6][C@@H:5]1[NH:7][C:8](=[O:20])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[N:15]1[N:16]=[CH:17][CH:18]=[N:19]1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of N-[(1S,2S)-4,4-difluoro-2-(2-methylpropane-2-sulfonamido)cyclopentyl]-2-(2H-1,2,3-triazol-2-yl)benzamide (1.7 g, 3.98 mmol) in DCM (100 ml) at 0° C. was added anisole (CAS number 100-66-3; 7.82 ml, 71.6 mmol) followed by the drop wise addition of trifluoromethanesulfonic acid in DCM (0.2M, 1.55 ml, 17.5 mmol). The reaction mixture was stirred at 0° C. for 1 hour and then at room temperature for 18 hours. The reaction mixture was quenched with sodium hydroxide (0.2M) until pH 11 obtained then extracted with DCM. The organics were filtered through a hydrophobic frit and concentrated in vacuo. The crude material was purified by SCX chromatography (2M ammonia in methanol) to afford the title compound.

Workup

waitat room temperature for 18 hours
customThe reaction mixture was quenched with sodium hydroxide (0.2M) until pH 11
customobtained
extractionthen extracted with DCM
filtrationThe organics were filtered through a hydrophobic frit
concentrationconcentrated in vacuo
customThe crude material was purified by SCX chromatography (2M ammonia in methanol)

Sources & evidence

ORD record: ord-0080dfd69fde4876b7fb4fa2481965af
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09156829B2

Reaction notes

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