Trifluoroacetic acid → HCID 178463564, compound

HRID 243458Notes

Reaction equation

C(OC([N:8]1[CH2:11][CH:10]([N:12]2[C:16]3[CH:17]=[C:18]([F:21])[CH:19]=[CH:20][C:15]=3[N:14]=[C:13]2[C@@H:22]([NH:24][C:25]2[N:33]=[CH:32][N:31]=[C:30]3[C:26]=2[N:27]=[CH:28][NH:29]3)[CH3:23])[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:8]1[CH2:9][CH:10]([N:12]2[C:16]3[CH:17]=[C:18]([F:21])[CH:19]=[CH:20][C:15]=3[N:14]=[C:13]2[CH:22]([NH:24][C:25]2[N:33]=[CH:32][N:31]=[C:30]3[C:26]=2[N:27]=[CH:28][NH:29]3)[CH3:23])[CH2:11]1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 3-{6-fluoro-2-[(S)-1-(9H-purin-6-ylamino)ethyl]benzoimidazol-1-yl}azetidine-1-carboxylic acid tert-butyl ester (214 mg, 0.47 mmol) in DCM (5 mL) at 0° C. was added TFA (1.7 mL) dropwise. The mixture was stirred at 0° C. for 20 min then slowly warmed to RT. Stirring was continued at RT for 1.5 h. The volatiles were removed under reduced pressure and the resulting residue was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined and concentrated in vacuo to afford 378 as a white solid (160 mg, 96%). LCMS (Method K): RT 1.73 min [M+H]+ 353.0. 1H NMR (DMSO-d6, 400 MHz): δ 8.25 (1H, br s), 8.17-8.07 (2H, m), 7.95 (1H, br s), 7.64 (1H, dd, J=8.82, 5.08 Hz), 7.08 (1H, td, J=9.27, 2.42 Hz), 5.80 (1H, br s), 5.63-5.53 (1H, m), 4.14-4.06 (1H, m), 4.01 (2H, d, J=7.20 Hz), 3.93-3.74 (2H, m), 1.63 (3H, d, J=6.71 Hz)

Workup

temperaturethen slowly warmed to RT
stirringStirring
waitwas continued at RT for 1.5 h
customThe volatiles were removed under reduced pressure
washwashed with MeOH
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-1d71693e6c8e4ed0aa09ac9ada80c6a7
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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