1,4-Dioxane → (R)-2-(6-Chloro-5-((4,4-difluorocyclohexyl)methylcarbamoyl)-1-oxoisoquinolin-2(1H)-yl)propyl acetate

HRID 418542Notes

Reaction equation

[C:1]([O:4][CH2:5][C@H:6]([N:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([Cl:19])[C:14]=2I)[C:9]1=[O:20])[CH3:7])(=[O:3])[CH3:2].Cl.[F:22][C:23]1([F:31])[CH2:28][CH2:27][CH:26]([CH2:29][NH2:30])[CH2:25][CH2:24]1.N12CCCN=C1CCCCC2.[O:43]1CCOC[CH2:44]1>[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:4][CH2:5][C@H:6]([N:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([Cl:19])[C:14]=2[C:44](=[O:43])[NH:30][CH2:29][CH:26]2[CH2:27][CH2:28][C:23]([F:31])([F:22])[CH2:24][CH2:25]2)[C:9]1=[O:20])[CH3:7])(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 110 °C

Procedure

A 5 mL process vial was charged with (R)-2-(6-chloro-5-iodo-1-oxoisoquinolin-2(1H)-yl)propyl acetate (18a) (400 mg, 0.0009 mol), (4,4-difluorocyclohexyl)methanamine hydrochloride (150 mg, 0.00081 mol), molybdenum hexacarbonyl (500 mg, 0.002 mol), palladium acetate (15 mg, 0.000067 mol), 1,8-diazabicyclo[5.4.0]undec-7-ene (500 mg, 0.003 mol) and 1,4-dioxane (4 mL, 0.04 mol). The vessel was sealed under air and stirred at 110° C. for 1 hour and cooled to room temperature. The mixture was concentrated and purified by flash chromatography to afford the desired product as a yellow oil. (143 mg, 37%).

Workup

customThe vessel was sealed under air
temperaturecooled to room temperature
concentrationThe mixture was concentrated
custompurified by flash chromatography

Sources & evidence

ORD record: ord-ec6ab1c9bac349bb8a8388064f558a01
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093265B2

Reaction notes

Loading…