[2-(difluoromethyl)phenyl]boronic acid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the procedure for Example 101 starting from tert-butyl N-[2-bromo-4-[[5-[(2S,5R,6S)-5-(tert-butoxycarbonylamino)-6-fluoro-oxepan-2-yl]-1-methyl-pyrazol-4-yl]carbamoyl]thiazol-5-yl]carbamate (Intermediate 95), and replacing 3,6-dihydro-2H-pyran-4-boronic acid pinacol ester with (2-(difluoromethyl)phenyl)boronic acid gave 335. 1H NMR (400 MHz, DMSO-d6) δ 9.05 (s, 1H), 8.09-7.80 (m, 1H), 7.77 (d, J=7.6 Hz, 1H), 7.71-7.66 (m, 2H), 7.65-7.59 (m, 1H), 7.59-7.50 (m, 3H), 4.75 (dd, J=10.6, 3.8 Hz, 1H), 4.42-4.26 (m, 1H), 4.19-4.07 (m, 1H), 4.04-3.87 (m, 1H), 3.79 (s, 3H), 3.21-3.08 (m, 1H), 2.08-1.99 (m, 1H), 1.97-1.85 (m, 1H), 1.74-1.58 (m, 4H). LCMS (ES+) m/z 481 (M+1).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the procedure for Example 101 starting from tert-butyl N-[2-bromo-4-[[5-[(2S,5R,6S)-5-(tert-butoxycarbonylamino)-6-fluoro-oxepan-2-yl]-1-methyl-pyrazol-4-yl]carbamoyl]thiazol-5-yl]carbamate (Intermediate 95), and replacing 3,6-dihydro-2H-pyran-4-boronic acid pinacol ester with (2-(difluoromethyl)phenyl)boronic acid gave 335. 1H NMR (400 MHz, DMSO-d6) δ 9.05 (s, 1H), 8.09-7.80 (m, 1H), 7.77 (d, J=7.6 Hz, 1H), 7.71-7.66 (m, 2H), 7.65-7.59 (m, 1H), 7.59-7.50 (m, 3H), 4.75 (dd, J=10.6, 3.8 Hz, 1H), 4.42-4.26 (m, 1H), 4.19-4.07 (m, 1H), 4.04-3.87 (m, 1H), 3.79 (s, 3H), 3.21-3.08 (m, 1H), 2.08-1.99 (m, 1H), 1.97-1.85 (m, 1H), 1.74-1.58 (m, 4H). LCMS (ES+) m/z 481 (M+1).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the procedure of Intermediate 104, replacing 2,6-difluoro-4-methoxyphenylboronic acid with (2-(difluoromethyl)phenyl)boronic acid gave the title compound.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Preparation 3 is prepared following the procedure described for preparation 1d, substituting 3-(trifluoromethyl)phenylboronic acid with 2-(difluoromethyl)phenylboronic acid and substituting preparation 1c with preparation 2b as starting material. ESI mass spectrum: [M+H]+=409; Retention time HPLC: 1.00 min (Z018_S04). Preparation 3 is prepared 1.00 min (Z018_S04)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Preparation 3 is prepared following the procedure described for preparation 1d, substituting 3-(trifluoromethyl)phenylboronic acid with 2-(difluoromethyl)phenylboronic acid and substituting preparation 1c with preparation 2b as starting material. ESI mass spectrum: [M+H]+=409; Retention time HPLC: 1.00 min (Z018_S04). Preparation 3 is prepared 1.00 min (Z018_S04)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the procedure for Example 101 starting from tert-butyl N-[2-bromo-4-[[5-[(2S,5R,6S)-5-(tert-butoxycarbonylamino)-6-fluoro-oxepan-2-yl]-1-methyl-pyrazol-4-yl]carbamoyl]thiazol-5-yl]carbamate (Intermediate 95), and replacing 3,6-dihydro-2H-pyran-4-boronic acid pinacol ester with (2-(difluoromethyl)phenyl)boronic acid gave 335. 1H NMR (400 MHz, DMSO-d6) δ 9.05 (s, 1H), 8.09-7.80 (m, 1H), 7.77 (d, J=7.6 Hz, 1H), 7.71-7.66 (m, 2H), 7.65-7.59 (m, 1H), 7.59-7.50 (m, 3H), 4.75 (dd, J=10.6, 3.8 Hz, 1H), 4.42-4.26 (m, 1H), 4.19-4.07 (m, 1H), 4.04-3.87 (m, 1H), 3.79 (s, 3H), 3.21-3.08 (m, 1H), 2.08-1.99 (m, 1H), 1.97-1.85 (m, 1H), 1.74-1.58 (m, 4H). LCMS (ES+) m/z 481 (M+1).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the procedure of Intermediate 104, replacing 2,6-difluoro-4-methoxyphenylboronic acid with (2-(difluoromethyl)phenyl)boronic acid gave the title compound.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Preparation 3 is prepared following the procedure described for preparation 1d, substituting 3-(trifluoromethyl)phenylboronic acid with 2-(difluoromethyl)phenylboronic acid and substituting preparation 1c with preparation 2b as starting material. ESI mass spectrum: [M+H]+=409; Retention time HPLC: 1.00 min (Z018_S04). Preparation 3 is prepared 1.00 min (Z018_S04)