Triphenylphosphine → (R)-4-((R)-1-(6-(1-tert-butyl-1H-pyrazol-4-yl)-3-(difluoromethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

HRID 2209006Notes

Reaction equation

[C:1]([N:5]1[CH:9]=[C:8]([C:10]2[NH:15][C:14](=[O:16])[C:13]3[N:17]([CH:20]([F:22])[F:21])[CH:18]=[N:19][C:12]=3[CH:11]=2)[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2].O[C@H:24]([C@H:26]1[CH2:30][N:29]([C@@H:31]([C:33]2[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=2)[CH3:32])[C:28](=[O:41])[CH2:27]1)[CH3:25].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1.C(Cl)Cl>[C:1]([N:5]1[CH:9]=[C:8]([C:10]2[N:15]=[C:14]([O:16][C@@H:24]([C@H:26]3[CH2:30][N:29]([C@@H:31]([C:33]4[CH:34]=[CH:35][C:36]([O:39][CH3:40])=[CH:37][CH:38]=4)[CH3:32])[C:28](=[O:41])[CH2:27]3)[CH3:25])[C:13]3[N:17]([CH:20]([F:21])[F:22])[CH:18]=[N:19][C:12]=3[CH:11]=2)[CH:7]=[N:6]1)([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 40 °C

Procedure

6-(1-tert-butyl-1H-pyrazol-4-yl)-3-(difluoromethyl)-3H-imidazo[4,5-c]pyridin-4(5H)-one 2.33 (33 mg, 0.107 mmol), lactam alcohol 1.05 (42 mg, 0.16 mmol), and PPh3 (44 mg, 0.17 mmol) were taken up in THF (1 mL). To the resulting suspension was added DEAD (26 μL, 0.17 mmol) dropwise. The resulting cloudy solution was heated to 40° C. and stirred 1.25 h. The solution was then diluted with DCM and concentrated directly onto silica gel. Purification by silica gel chromatography (15% to 60% acetone in hexanes) afforded (R)-4-((R)-1-(6-(1-tert-butyl-1H-pyrazol-4-yl)-3-(difluoromethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 2.34 that was used without further purification.

Workup

concentrationconcentrated directly onto silica gel
customPurification by silica gel chromatography (15% to 60% acetone in hexanes)

Sources & evidence

ORD record: ord-f46f09b5625a492a95b6d759b71c1498
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09376441B2

Reaction notes

Loading…