Trifluoroacetic acid → (+/-)-4'-(5-chloro-4-(2-oxoazepan-3-ylamino)pyrimidin-2-ylamino)-5'-fluoro-N,2'-dimethylbiphenyl-4-carboxamide

HRID 2091953Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH2:15][CH2:14][CH2:13][CH2:12][NH:11][C:10]2=[O:16])[C:5]([Cl:17])=[CH:4][N:3]=1.[NH2:18][C:19]1[C:24]([F:25])=[CH:23][C:22]([C:26]2[CH:31]=[CH:30][C:29]([C:32]([NH:34][CH3:35])=[O:33])=[CH:28][CH:27]=2)=[C:21]([CH3:36])[CH:20]=1.C(O)(C(F)(F)F)=O>CC(O)C>[Cl:17][C:5]1[C:6]([NH:8][CH:9]2[CH2:15][CH2:14][CH2:13][CH2:12][NH:11][C:10]2=[O:16])=[N:7][C:2]([NH:18][C:19]2[C:24]([F:25])=[CH:23][C:22]([C:26]3[CH:27]=[CH:28][C:29]([C:32]([NH:34][CH3:35])=[O:33])=[CH:30][CH:31]=3)=[C:21]([CH3:36])[CH:20]=2)=[N:3][CH:4]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 3-(2,5-dichloropyrimidin-4-ylamino)azepan-2-one (Intermediate 16, 28 mg, 0.10 mmol), 4′-Amino-5′-fluoro-N,2′-dimethylbiphenyl-4-carboxamide (Intermediate 17, 31 mg, 0.12 mmol, 1.2 equiv.) and TFA (37 μL, 57 mg, 0.50 mmol, 5 equiv.) in 2-propanol (3 mL) is stirred in a sealed tube at 100° C. for 48 h. The resulting solution is concentrated and then purified by preparative RP-HPLC to afford (±)-4′-(5-chloro-4-(2-oxoazepan-3-ylamino)pyrimidin-2-ylamino)-5′-fluoro-N,2′-dimethylbiphenyl-4-carboxamide; ESMS m/z 497.2 (M+H+).

Workup

concentrationThe resulting solution is concentrated
custompurified by preparative RP-HPLC

Sources & evidence

ORD record: ord-597f940e7fb24ef48bb3800dcf61ecfc
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08440681B2

Reaction notes

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