Lithium Chloride → 5-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595601Notes

Reaction equation

HRID 595601 reaction equation
Br[C:2]1[C:3]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:24])=[O:23])=[CH:4][C:5]2[O:9][C:8]([C:10]3[O:11][C:12]([CH3:15])=[N:13][N:14]=3)=[C:7]([C:16]([NH:18][CH3:19])=[O:17])[C:6]=2[CH:20]=1.[F:27][C:28]1[C:29]2[CH:30]=[C:31]3[C:40]4[N:41]=[C:42]([Sn](C)(C)C)[CH:43]=[CH:44][C:39]=4[O:38][CH2:37][N:32]3[C:33]=2[CH:34]=[CH:35][CH:36]=1.[Li+].[Cl-]>CC(O)C>[F:27][C:28]1[C:29]2[CH:30]=[C:31]3[C:40]4[N:41]=[C:42]([C:2]5[C:3]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:24])=[O:23])=[CH:4][C:5]6[O:9][C:8]([C:10]7[O:11][C:12]([CH3:15])=[N:13][N:14]=7)=[C:7]([C:16]([NH:18][CH3:19])=[O:17])[C:6]=6[CH:20]=5)[CH:43]=[CH:44][C:39]=4[O:38][CH2:37][N:32]3[C:33]=2[CH:34]=[CH:35][CH:36]=1

Participants

5

Reactant 3

HCID 433294Lithium ChlorideHCID 8672829411-fluoro-2-(trimethylstannyl)-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indoleHCID 903335625-bromo-N-methyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

Product 1

HCID 778461445-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideYield 21%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of compound 5-bromo-N-methyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (70 mg, 0.16 mmol), 11-fluoro-2-(trimethylstannyl)-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (95 mg, 0.24 mmol) and LiCl (20 mg, 0.47 mmol) in IPA (2 mL), chloro[(tricyclohexylphosphine)-2-(2′-aminobiphenyl)]palladium(II) (50 mg) was added under N2 protection. After stirring at 100° C. overnight, the reaction mixture was concentrated in vacuo. The residue was purified by prep-TLC (DCM:MeOH=100:1) to give the product of 5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (20 mg, yield: 21%). 1H-NMR (CDCl3, 400 MHz) δ 9.81 (br s, 1H), 8.81 (s, 1H), 7.77 (s, 1H), 7.55˜7.46 (m, 2H), 7.25˜7.18 (m, 2H), 7.13 (s, 1H), 6.89˜6.80 (m, 1H), 6.01 (s, 2H), 3.41 (s, 3H), 3.09 (d, J=4.4 Hz, 3H), 2.76 (s, 3H), 2.68 (s, 3H). MS (M+H)+: 603.

Workup

  1. additionwas added under N2 protection
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. customThe residue was purified by prep-TLC (DCM:MeOH=100:1)

Sources & evidence

ORD record
ord-3afd011482904f088a9ff119218ca2ca
Source dataset
uspto-grants-2016_01
Patent number
US09242998B2

Reaction notes

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