5-bromo-2-(4-fluorophenyl)-N-methyl-6-(2-oxopyrrolidin-1-yl)benzofuran-3-carboxamide → 5-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(2-oxopyrrolidin-1-yl)benzofuran-3-carboxamide

HRID 1776918Notes

Reaction equation

HRID 1776918 reaction equation
[F:1][C:2]1[C:3]2[CH:4]=[C:5]3[C:14]4[N:15]=[C:16]([Sn](C)(C)C)[CH:17]=[CH:18][C:13]=4[O:12][CH2:11][N:6]3[C:7]=2[CH:8]=[CH:9][CH:10]=1.Br[C:24]1[C:25]([N:44]2[CH2:48][CH2:47][CH2:46][C:45]2=[O:49])=[CH:26][C:27]2[O:31][C:30]([C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=3)=[C:29]([C:39]([NH:41][CH3:42])=[O:40])[C:28]=2[CH:43]=1>CN(C=O)C.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>[F:1][C:2]1[C:3]2[CH:4]=[C:5]3[C:14]4[N:15]=[C:16]([C:24]5[C:25]([N:44]6[CH2:48][CH2:47][CH2:46][C:45]6=[O:49])=[CH:26][C:27]6[O:31][C:30]([C:32]7[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=7)=[C:29]([C:39]([NH:41][CH3:42])=[O:40])[C:28]=6[CH:43]=5)[CH:17]=[CH:18][C:13]=4[O:12][CH2:11][N:6]3[C:7]=2[CH:8]=[CH:9][CH:10]=1

Participants

5

Reactant 2

HCID 712951155-bromo-2-(4-fluorophenyl)-N-methyl-6-(2-oxopyrrolidin-1-yl)benzofuran-3-carboxamideHCID 8672829411-fluoro-2-(trimethylstannyl)-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indole

Product 1

HCID 715092535-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(2-oxopyrrolidin-1-yl)benzofuran-3-carboxamideYield 30.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 178418397HCID 178418397, compoundSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 11-fluoro-2-(trimethylstannyl)-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (60 mg, 0.14 mmol), 5-bromo-2-(4-fluorophenyl)-N-methyl-6-(2-oxopyrrolidin-1-yl)benzofuran-3-carboxamide (50 mg, 0.11 mmol) in DMF (4 mL), Pd(PPh3)4 was added. The reaction mixture was stirred at 100° C. overnight. The reaction mixture was filtered through a Celit pad. The filtrate was concentrated in vacuo. The resulting residue was suspended in water, extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using prep-HPLC to provide 5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(2-oxopyrrolidin-1-yl)benzofuran-3-carboxamide (20 mg, yield: 29.2%). 1H-NMR (CDCl3, 400 MHz) δ 7.97 (s, 1H), 7.89˜7.93 (m, 2H), 7.44 (s, 1H), 7.40˜7.42 (m, 2H), 7.11˜7.19 (m, 4H), 7.05 (d, J=8.8 Hz, 1H), 6.77˜6.82 (m, 1H), 5.92 (s, 2H), 5.85 (br s, 1H), 3.83 (t, J=7.2 Hz, 2H), 2.95 (d, J=4.8 Hz, 3H), 2.26 (t, J=8.4 Hz, 2H), 2.00˜2.06 (m, 2H). MS (M+H)+: 591.

Workup

  1. filtrationThe reaction mixture was filtered through a Celit pad
  2. concentrationThe filtrate was concentrated in vacuo
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified

Sources & evidence

ORD record
ord-18d6e84d7e5f4dad94d23959a61cc1dd
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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