Diisopropylethylamine → (R)-5-bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-((trifluoromethyl)thio)phenyl)nicotinamide

HRID 73755Notes

Reaction equation

CCN(C(C)C)C(C)C.[Br:10][C:11]1[C:12](Cl)=[N:13][CH:14]=[C:15]([CH:30]=1)[C:16]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([S:25][C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=1)=[O:17].[NH:32]1[CH2:36][CH2:35][C@@H:34]([OH:37])[CH2:33]1>CC(O)C.CCOC(C)=O>[Br:10][C:11]1[C:12]([N:32]2[CH2:36][CH2:35][C@@H:34]([OH:37])[CH2:33]2)=[N:13][CH:14]=[C:15]([CH:30]=1)[C:16]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([S:25][C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=1)=[O:17]

Participants

Conditions

Temperature: 140 °C

Procedure

DIPEA (73 μL, 0.42 mmol) was added to a solution of 5-bromo-6-chloro-N-(4-((trifluoromethyl)thio)phenyl)nicotinamide (Stage 11.2, 123 mg, 0.3 mmol) and (R)-pyrrolidin-3-ol (31.4 mg, 0.36 mmol) in iPrOH (300 μL) in a vial, which was sealed and heated at 140° C. for 1 h. After cooling at RT, the RM was diluted with EtOAc, washed with brine, dried over Na2SO4 and the solvent evaporated off under reduced pressure to give a residue which was triturated with iPr2O, filtered and dried to afford the title compound as a white crystalline powder. HPLC (Condition 4) tR=5.9 min, UPLC-MS (Condition 3) tR=1.21 min, m/z=464.1 [M+H]+.

Workup

customwas sealed
temperatureAfter cooling at RT
washwashed with brine
dry with materialdried over Na2SO4
customthe solvent evaporated off under reduced pressure
customto give a residue which
customwas triturated with iPr2O
filtrationfiltered
customdried

Sources & evidence

ORD record: ord-1ad54c7ce1de415d8e8537335f039a36
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08829195B2

Reaction notes

Loading…