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

HRID 595574Notes

Reaction equation

HRID 595574 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[CH2:11][CH2:12][S:13][CH2:14][CH:15]=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>O1CCOCC1.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>[S:13]1[CH2:14][CH:15]=[C:10]([C:8]2[O:9][C:5]3[CH:4]=[C:3]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:24])=[O:23])[C:2]([C:42]4[CH:43]=[CH:44][C:39]5[O:38][CH2:37][N:32]6[C:33]7[CH:34]=[CH:35][CH:36]=[C:28]([F:27])[C:29]=7[CH:30]=[C:31]6[C:40]=5[N:41]=4)=[CH:20][C:6]=3[C:7]=2[C:16]([NH:18][CH3:19])=[O:17])[CH2:11][CH2:12]1

Participants

5

Reactant 2

HCID 8672829411-fluoro-2-(trimethylstannyl)-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indoleHCID 90332468HCID 90332468, compound

Product 1

HCID 778456652-(3,6-dihydro-2H-thiopyran-4-yl)-5-(11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideYield 12.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 5-bromo-2-(3,6-dihydro-2H-thiopyran-4-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (100 mg, 0.2 mmol), 11-fluoro-2-(trimethylstannyl)-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (105 mg, 0.26 mmol) in 1,4-dioxane (5 mL) was added Pd(PPh3)4(10 mg) under nitrogen. The reaction mixture was heated at 100° C. overnight, concentrated in vacuo to remove 1,4-dioxane and purified by prep-TLC (PE:EA=1:1) to give 2-(3,6-dihydro-2H-thiopyran-4-yl)-5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (15 mg, yield: 11%). 1H-NMR (CDCl3, 400 MHz) δ 7.97 (s, 1H), 7.58 (s, 1H), 7.47 (s, 2H), 7.18˜7.23 (m, 2H), 7.11 (d, J=8.4 Hz, 1H), 6.80˜6.86 (m, 2H), 6.05 (d, J=4.8 Hz, 1H), 5.99 (s, 2H), 3.41 (t, J=2.0 Hz, 2H), 3.35 (s, 3H), 3.00 (d, J=4.8 Hz, 3H), 2.90 (t, J=5.6 Hz, 2H), 2.80 (d, J=3.2 Hz, 2H), 2.71 (s, 3H). MS (M+H)+: 619.

Workup

  1. concentrationconcentrated in vacuo
  2. customto remove 1,4-dioxane
  3. custompurified by prep-TLC (PE:EA=1:1)

Sources & evidence

ORD record
ord-a3de9ddf60864d20ba5f0f016d61c9ed
Source dataset
uspto-grants-2016_01
Patent number
US09242998B2

Reaction notes

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