Potassium Phosphate, Tribasic → 4-Fluoro-2-(5-(5-(3-(fluoromethyl)-4-methylpiperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-6-(1-oxo-3,4,6,7,8,9-hexa-hydropyrazino[1,2-a]indol-2(1H)-yl)benzyl acetate

HRID 1026432Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][N:20]([CH3:23])[CH:19]([CH2:24][F:25])[CH2:18]3)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:26]([O:29][CH2:30][C:31]1[C:36](B2OC(C)(C)C(C)(C)O2)=[CH:35][C:34]([F:46])=[CH:33][C:32]=1[N:47]1[CH2:59][CH2:58][N:50]2[C:51]3[CH2:52][CH2:53][CH2:54][CH2:55][C:56]=3[CH:57]=[C:49]2[C:48]1=[O:60])(=[O:28])[CH3:27].[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:26]([O:29][CH2:30][C:31]1[C:32]([N:47]2[CH2:59][CH2:58][N:50]3[C:51]4[CH2:52][CH2:53][CH2:54][CH2:55][C:56]=4[CH:57]=[C:49]3[C:48]2=[O:60])=[CH:33][C:34]([F:46])=[CH:35][C:36]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][N:20]([CH3:23])[CH:19]([CH2:24][F:25])[CH2:18]3)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1)(=[O:28])[CH3:27]

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 111g (1 g, 2.4 mmol), 4-fluoro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate (1.3 g, 2.68 mmol), PdCl2(dppf) (190 mg, 0.24 mmol), K3PO4 (1 g, 4.8 mmol), and NaOAc (390 mg, 4.8 mmol) in MeCN (15 mL) and H2O (1.5 mL) was heated at 110° C. for 3 h. The solvent was evaporated in vacuo. The residue was purified on silica gel column (DCM: MeOH=50:1) to give 111h (0.8 g, yield 45%).

Workup

customThe solvent was evaporated in vacuo
customThe residue was purified on silica gel column (DCM: MeOH=50:1)

Sources & evidence

ORD record: ord-6049040b47384218be76dededf819b05
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08729072B2

Reaction notes

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