Potassium Phosphate, Tribasic → 2-(5-(6,7-Dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-fluoro-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl Acetate

HRID 1918889Notes

Reaction equation

[C:1]([O:4][CH2:5][C:6]1[C:11](N2CCN3C4CCCCC=4C=C3C2=O)=[CH:10][C:9]([F:26])=[CH:8][C:7]=1[N:27]1[CH2:39][CH2:38][N:30]2[C:31]3[CH2:32][CH2:33][CH2:34][CH2:35][C:36]=3[CH:37]=[C:29]2[C:28]1=[O:40])(=[O:3])[CH3:2].Br[C:42]1[CH:43]=[C:44]([NH:50][C:51]2[CH:59]=[C:54]3[CH2:55][O:56][CH2:57][CH2:58][N:53]3[N:52]=2)[C:45](=[O:49])[N:46]([CH3:48])[CH:47]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC([O-])=O.[Na+]>CC#N.O.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:1]([O:4][CH2:5][C:6]1[C:7]([N:27]2[CH2:39][CH2:38][N:30]3[C:31]4[CH2:32][CH2:33][CH2:34][CH2:35][C:36]=4[CH:37]=[C:29]3[C:28]2=[O:40])=[CH:8][C:9]([F:26])=[CH:10][C:11]=1[C:42]1[CH:43]=[C:44]([NH:50][C:51]2[CH:59]=[C:54]3[CH2:55][O:56][CH2:57][CH2:58][N:53]3[N:52]=2)[C:45](=[O:49])[N:46]([CH3:48])[CH:47]=1)(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 2-(acetoxymethyl)-5-fluoro-3-(1-oxo-3,4,6,7,8,9-hexahydro-pyrazino[1,2-a]indol-2(1H)-yl)phenylboronic acid 210d (150 mg, 0.38 mmol), 5-bromo-3-(6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-ylamino)-1-methylpyridin-2(1H)-one 110c (122 mg, 0.38 mmol), PdCl2(dppf) (41 mg, 0.056 mmol), K3PO4 (100 mg), and NaOAc (50 mg) in MeCN (10 mL) and H2O (3 mL) was heated at 110° C. in a sealed tube for 2 h. The solvent was evaporated in vacuo and the residue was purified on reverse phase Combi-flash to give 149a (120 mg, 53%). MS: [M+H]+ 601.

Workup

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

Sources & evidence

ORD record: ord-919a632fb6314885813b571910795f2d
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08618107B2

Reaction notes

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