Diethylamine → tert-butyl N-[(3R)-1-methyl-3-[3-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]prop-2-ynyl]-2-oxo-pyrrolidin-3-yl]carbamate

HRID 626887Notes

Reaction equation

[CH3:1][N:2]1[CH2:6][CH2:5][C@:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])([CH2:7][C:8]#[CH:9])[C:3]1=[O:18].I[C:20]1[N:25]=[C:24]([CH3:26])[CH:23]=[C:22]([C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=2)[N:21]=1.N(CC)CC>C1COCC1.[Cu](I)I>[CH3:1][N:2]1[CH2:6][CH2:5][C@:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:15])([CH3:14])[CH3:16])([CH2:7][C:8]#[C:9][C:20]2[N:25]=[C:24]([CH3:26])[CH:23]=[C:22]([C:27]3[CH:28]=[CH:29][C:30]([C:33]([F:36])([F:34])[F:35])=[CH:31][CH:32]=3)[N:21]=2)[C:3]1=[O:18]

Participants

Conditions

Temperature: 20 °C

Procedure

Copper iodide (22.64 mg, 0.1200 mmol), followed by PdCl2(Ph3P)2 (41.73 mg, 0.060 mmol) was added portionwise to a solution of tert-butyl N-[(3R)-1-methyl-2-oxo-3-prop-2-ynyl-pyrrolidin-3-yl]carbamate (which may be prepared as described in Description 10) (300 mg, 1.19 mmol), 2-iodo-4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidine (which may be prepared as described in Description 12) (584.44 mg, 1.61 mmol) and Et2NH (0.62 mL, 5.95 mmol) in THF (10 mL) under N2 and the reaction was stirred at 20° C. for 18 hrs. The solvent was evaporated and the residue was purified by Biotage SP4, using a 25 g SNAP cartridge, eluting with 0 to 100% EtOAc/i-hexane affording tert-butyl N-[(3R)-1-methyl-3-[3-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]prop-2-ynyl]-2-oxo-pyrrolidin-3-yl]carbamate (D13) (482 mg, 0.987 mmol, 83.0% yield) as a pale yellow foam.

Workup

customThe solvent was evaporated
customthe residue was purified by Biotage SP4
washeluting with 0 to 100% EtOAc/i-hexane

Sources & evidence

ORD record: ord-e3bfe86a912a498b9c78be338fafb48d
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309254B2

Reaction notes

Loading…