Cesium carbonate → 5-(11'-fluoro-6'H-spiro[cyclopropane-1,5'-indolo[1,2-h][1,7]naphthyridin]-2'-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595777Notes

Reaction equation

HRID 595777 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:9]([N:28]([CH3:33])[S:29]([CH3:32])(=[O:31])=[O:30])=[CH:10][C:11]3[O:15][C:14]([C:16]4[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=4)=[C:13]([C:23]([NH:25][CH3:26])=[O:24])[C:12]=3[CH:27]=2)[CH:5]=[CH:4][C:3]=1[C:34]1([CH2:37]O)[CH2:36][CH2:35]1.[F:39][C:40]1[CH:48]=[CH:47][CH:46]=[C:45]2[C:41]=1[CH:42]=[C:43](B1OC(C)(C)C(C)(C)O1)[NH:44]2.C([O-])([O-])=O.[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O1CCOCC1.O>[F:39][C:40]1[C:41]2[CH:42]=[C:43]3[C:2]4[N:7]=[C:6]([C:8]5[C:9]([N:28]([CH3:33])[S:29]([CH3:32])(=[O:30])=[O:31])=[CH:10][C:11]6[O:15][C:14]([C:16]7[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=7)=[C:13]([C:23]([NH:25][CH3:26])=[O:24])[C:12]=6[CH:27]=5)[CH:5]=[CH:4][C:3]=4[C:34]4([CH2:35][CH2:36]4)[CH2:37][N:44]3[C:45]=2[CH:46]=[CH:47][CH:48]=1

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 532172124-Fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-indoleHCID 903324785-(6-chloro-5-(1-(hydroxymethyl)cyclopropyl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

Product 1

HCID 903339085-(11'-fluoro-6'H-spiro[cyclopropane-1,5'-indolo[1,2-h][1,7]naphthyridin]-2'-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideYield 5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-(6-chloro-5-(1-(hydroxymethyl)cyclopropyl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (80 mg, 0.143 mmol) and 4-fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (56.1 mg, 0.215 mmol) in 1,4-Dioxane (2 mL) and water (20 μL) was added Cs2CO3 (93 mg, 0.287 mmol) and DTBPF PdCl2 (21 mg, 0.032 mmol). The mixture was heated to 80° C., stirred overnight, concentrated in vacuo and dried. The residue was dissolved in DCM (2.00 mL), followed by addition of triphenylphosphine (94 mg, 0.358 mmol) and DIAD (0.070 mL, 0.358 mmol). The mixture was stirred at RT for 4 h. Preparative TLC (eluted with 20% ethyl acetate in DCM) gave 5-(11′-fluoro-6′H-spiro[cyclopropane-1,5′-indolo[1,2-h][1,7]naphthyridin]-2′-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (4.5 mg, yield: 5%) MS (M+H)+: 639.

Workup

  1. concentrationconcentrated in vacuo
  2. customdried
  3. dissolutionThe residue was dissolved in DCM (2.00 mL)
  4. stirringThe mixture was stirred at RT for 4 h
  5. washPreparative TLC (eluted with 20% ethyl acetate in DCM)

Sources & evidence

ORD record
ord-d550062794c14c15ae004fd05eedff87
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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