N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide → HCID 44234537, compound

HRID 383564Notes

Reaction equation

[CH:1]1([NH:4][C:5](=[O:23])[C:6]2[CH:11]=[C:10](B3OC(C)(C)C(C)(C)O3)[C:9]([CH3:21])=[C:8]([F:22])[CH:7]=2)[CH2:3][CH2:2]1.Br[C:25]1[C:26](=[O:43])[N:27]([CH3:42])[C:28]2[N:33]([C:34]3[C:39]([F:40])=[CH:38][CH:37]=[CH:36][C:35]=3[F:41])[N:32]=[CH:31][C:29]=2[N:30]=1>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O>[CH:1]1([NH:4][C:5](=[O:23])[C:6]2[CH:7]=[C:8]([F:22])[C:9]([CH3:21])=[C:10]([C:25]3[C:26](=[O:43])[N:27]([CH3:42])[C:28]4[N:33]([C:34]5[C:39]([F:40])=[CH:38][CH:37]=[CH:36][C:35]=5[F:41])[N:32]=[CH:31][C:29]=4[N:30]=3)[CH:11]=2)[CH2:2][CH2:3]1

Participants

Conditions

Temperature: 125 °C

Procedure

A mixture of N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (520 mg, 1.63 mmol), 5-bromo-1-(2,6-difluorophenyl)-7-methyl-1H-pyrazolo[4,3-b]pyrazin-6(7H)-one (505 mg, 1.48 mmol) in 3.5 mL of dioxane and 1.5 mL of 2 N Na2CO3 was heated in a microwave at 125° C. for 25 min. It was diluted with EtOAc and washed with 1 N NaOH. The EtOAc layer was separated, dried and concentrated. Purification of the crude material on an ISCO 40 g column (with 30-75% EtOAc in Hexanes) provided N-cyclopropyl-3-(1-(2,6-difluorophenyl)-7-methyl-6-oxo-6,7-dihydro-1H-pyrazolo[4,3-b]pyrazin-5-yl)-5-fluoro-4-methylb enzamide as an off white amorphous solid. MS (ES+): 454.1 (M+H)+.

Workup

washwashed with 1 N NaOH
customThe EtOAc layer was separated
customdried
concentrationconcentrated
customPurification of the crude material on an ISCO 40 g column (with 30-75% EtOAc in Hexanes)

Sources & evidence

ORD record: ord-16f4b542603d40a88ad7e9c4db83f3e6
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08367671B2

Reaction notes

Loading…