Cesium carbonate → 6-Chloro-2-methyl-4-(5-(oxetan-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl amino)pyridazin-3(2H)-one

HRID 407808Notes

Reaction equation

[O:1]1[CH2:4][CH:3]([N:5]2[CH2:10][CH2:9][N:8]3[N:11]=[C:12]([NH2:14])[CH:13]=[C:7]3[CH2:6]2)[CH2:2]1.Br[C:16]1[C:17](=[O:24])[N:18]([CH3:23])[N:19]=[C:20]([Cl:22])[CH:21]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Cl:22][C:20]1[CH:21]=[C:16]([NH:14][C:12]2[CH:13]=[C:7]3[CH2:6][N:5]([CH:3]4[CH2:4][O:1][CH2:2]4)[CH2:10][CH2:9][N:8]3[N:11]=2)[C:17](=[O:24])[N:18]([CH3:23])[N:19]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (25 mL), 155b (640 mg, 3.3 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (1.1 g, 4.95 mmol), Pd2(dba)3 (302 mg, 0.33 mmol), XantPhos (381 mg, 0.66 mmol), and cesium carbonate (2.15 g, 6.6 mmol). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 3 h. After this time the reaction was cooled to room temperature. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was washed with ethyl acetate to afford 155c (754 mg, 68%) as a yellow solid. MS-ESI: [M+H]+ 337.3

Workup

customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
customAfter three cycles of vacuum/argon flush
temperatureAfter this time the reaction was cooled to room temperature
filtrationIt was then filtered
customthe filtrate was evaporated under reduced pressure
washThe residue was washed with ethyl acetate

Sources & evidence

ORD record: ord-dc376fb0973843ff9e0b0581cd37a121
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754077B2

Reaction notes

Loading…