Diisopropylethylamine → 5-bromo-6-(3-hydroxyazetidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 525698Notes

Reaction equation

CCN(C(C)C)C(C)C.[Br:10][C:11]1[C:12]([N:31]2C[CH2:34][C@@H:33]([OH:36])[CH2:32]2)=[N:13][CH:14]=[C:15]([CH:30]=1)[C:16]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=1)=[O:17].Cl.OC1CNC1>CC(O)C.CCOC(C)=O>[Br:10][C:11]1[C:12]([N:31]2[CH2:34][CH:33]([OH:36])[CH2:32]2)=[N:13][CH:14]=[C:15]([CH:30]=1)[C:16]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][C:26]([F:29])([F:27])[F:28])=[CH:21][CH:20]=1)=[O:17]

Participants

Conditions

Temperature: 140 °C

Procedure

DIPEA (3.67 mL, 21.0 mmol) was added to (R)-5-Bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 6.2, 2.77 g, 7.0 mmol) and 3-hydroxyazetidine HCl (0.920 g, 8.40 mmol) in iPrOH (7.0 mL) in a vial which was sealed and the RM mixture was stirred at 140° C. for 1.5 h. After cooling to RT, the RM was dissolved in EtOAc, washed with brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give the title product as a yellow foam. HPLC (Condition 4) tR=5.37 min, UPLC-MS (Condition 3) tR=1.09 min, m/z=432/434 [M+H]+.

Workup

customwas sealed
temperatureAfter cooling to RT
washwashed with brine
dry with materialdried over Na2SO4
customthe solvent was evaporated off under reduced pressure

Sources & evidence

ORD record: ord-8f237456798d4b90a3e452701a6e8c5a
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09340537B2

Reaction notes

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