1,2-Dimethoxyethane → 4-fluoro-2-(1-methyl-5-(5-(1-methylpyrrolidin-2-yl)pyridin-2-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 1918984Notes

Reaction equation

HRID 1918984 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:56]=[CH:55][C:54]([CH:57]3[CH2:61][CH2:60][CH2:59][N:58]3[CH3:62])=[CH:53][N:52]=2)[C:45](=[O:49])[N:46]([CH3:48])[CH:47]=1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.CO>[C:1]([O:4][CH2:5][C:6]1[C:7]([N:27]2[CH2:39][CH2:38][N:30]3[C:35]4[CH2:34][CH2:33][CH2:32][CH2:31][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:56]=[CH:55][C:54]([CH:57]3[CH2:61][CH2:60][CH2:59][N:58]3[CH3:62])=[CH:53][N:52]=2)[C:45](=[O:49])[N:46]([CH3:48])[CH:47]=1)(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 580439935-Bromo-1-methyl-3-(5-(1-methylpyrrolidin-2-yl)pyridin-2-ylamino)pyridin-2(1H)-oneHCID 670164654-fluoro-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl acetate

Product 1

HCID 670162034-fluoro-2-(1-methyl-5-(5-(1-methylpyrrolidin-2-yl)pyridin-2-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 acetateYield 62.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21226129Dichloromethane methanolSolvent

Procedure

Following Example 121b, 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 210d (338 mg, 0.7 mmol), 202a (181 mg, 0.5 mmol), 1M sodium carbonate solution (2 mL, 2 mmol), tetrakis(triphenylphosphine)palladium(0) (29 mg, 0.025 mmol) and 1,2-dimethoxyethane (5 mL) were reacted. Work-up and flash column chromatography (silica, 3:1 methylene chloride/methanol) give a mixture (200 mg) of 4-fluoro-2-(1-methyl-5-(5-(1-methylpyrrolidin-2-yl)pyridin-2-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 and 202 as a yellow residue.

Workup

  1. customwere reacted

Sources & evidence

ORD record
ord-55e83f7bab004997b8c2e5e266e20892
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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