Sodium Carbonate → 4-Fluoro-2-(1-methyl-5-(5-methyl-1H-pyrazol-3-ylamino)-6-oxo-1,6-dihydropyridin-3-yl)-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-benzyl acetate

HRID 1918846Notes

Reaction equation

[CH3:1][N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:4]([NH:17][C:18]2[CH:22]=[C:21]([CH3:23])[NH:20][N:19]=2)[C:3]1=[O:24].[C:25]([O:28][CH2:29][C:30]1[C:35]([N:36]2[CH2:48][CH2:47][N:39]3[C:40]4[CH2:41][CH2:42][CH2:43][CH2:44][C:45]=4[CH:46]=[C:38]3[C:37]2=[O:49])=[CH:34][C:33]([F:50])=[CH:32][C:31]=1Br)(=[O:27])[CH3:26].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:25]([O:28][CH2:29][C:30]1[C:35]([N:36]2[CH2:48][CH2:47][N:39]3[C:40]4[CH2:41][CH2:42][CH2:43][CH2:44][C:45]=4[CH:46]=[C:38]3[C:37]2=[O:49])=[CH:34][C:33]([F:50])=[CH:32][C:31]=1[C:6]1[CH:5]=[C:4]([NH:17][C:18]2[CH:22]=[C:21]([CH3:23])[NH:20][N:19]=2)[C:3](=[O:24])[N:2]([CH3:1])[CH:7]=1)(=[O:27])[CH3:26]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 124a (330 mg, 1 mmol), 2-bromo-4-fluoro-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl acetate 197d (434 mg, 1 mmol), PdCl2(dppf) (82 mg, 0.1 mmol), 2.0M Na2CO3 (2.0 equiv) in DME (10 mL) was heated at 120° C. under microwave irradiation for 0.5 h. The solvent was evaporated in vacuo. The residue was purified on reverse phase Combi-flash to give the title compound (160 mg, 29%). LCMS: [M+H]+ 559

Workup

customThe solvent was evaporated in vacuo
customThe residue was purified on reverse phase Combi-flash

Sources & evidence

ORD record: ord-f8bf0a81b6c6436c81f0cb2ae4b278ea
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08618107B2

Reaction notes

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