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

HRID 1776863Notes

Reaction equation

HRID 1776863 reaction equation
[N:1]([CH2:4][CH:5]1[N:10]2[C:11]3[CH:12]=[CH:13][CH:14]=[C:15]([F:18])[C:16]=3[CH:17]=[C:9]2[C:8]2[N:19]=[C:20](Cl)[CH:21]=[CH:22][C:7]=2[O:6]1)=[N+:2]=[N-:3].[F:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[O:32][C:33]3[CH:43]=[C:42]([N:44]([CH3:49])[S:45]([CH3:48])(=[O:47])=[O:46])[C:41](B4OC(C)(C)C(C)(C)O4)=[CH:40][C:34]=3[C:35]=2[C:36]([NH:38][CH3:39])=[O:37])=[CH:27][CH:26]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CCOC(C)=O>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:1]([CH2:4][CH:5]1[N:10]2[C:11]3[CH:12]=[CH:13][CH:14]=[C:15]([F:18])[C:16]=3[CH:17]=[C:9]2[C:8]2[N:19]=[C:20]([C:41]3[C:42]([N:44]([CH3:49])[S:45]([CH3:48])(=[O:47])=[O:46])=[CH:43][C:33]4[O:32][C:31]([C:28]5[CH:29]=[CH:30][C:25]([F:24])=[CH:26][CH:27]=5)=[C:35]([C:36]([NH:38][CH3:39])=[O:37])[C:34]=4[CH:40]=3)[CH:21]=[CH:22][C:7]=2[O:6]1)=[N+:2]=[N-:3]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 867282666-(azidomethyl)-2-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indole

Product 1

HCID 867282675-(6-(azidomethyl)-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

To a mixture of 6-(azidomethyl)-2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (1.4 g, 4.25 mmol), 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (1.8 g, 3.73 mmol) and K3PO4.3H2O (3.4 g, 12.75 mmol) in Dioxane/water (10 mL/1 mL), Pd2(dba)3 (195 mg, 0.21 mmol) and X-Phos (200 mg, 0.42 mmol) were added. The reaction mixture was stirred at 90° C. for 2 hours under N2 protection. Then cooled to room temperature and added EtOAc, then filtered through a Celite pad. The combined organic phase was washed with water and brine, dried over Na2SO4. The solvent was concentrated in vacuo giving 5-(6-(azidomethyl)-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide. The crude product was used in the next step without purification. 1H-NMR (CDCl3, 400 MHz) δ 2.73 (s, 3H), 2.97˜3.03 (d, J=4.8 Hz, 3H), 3.04˜3.15 (d, J=10.8 Hz, 1H), 3.20˜3.32 (m, 1H), 3.40 (s, 3H), 5.93˜6.02 (m, 1H), 6.33˜6.40 (m, 1H), 6.81˜6.89 (m, 1H), 7.14˜7.26 (m, 5H), 7.45˜7.53 (m, 2H), 7.67 (s, 1H), 7.93˜8.01 (m, 2H), 8.03 (s, 1H). MS (M+H)+: 670.

Workup

  1. additionwere added
  2. temperatureThen cooled to room temperature
  3. filtrationfiltered through a Celite pad
  4. washThe combined organic phase was washed with water and brine
  5. dry with materialdried over Na2SO4
  6. concentrationThe solvent was concentrated in vacuo

Sources & evidence

ORD record
ord-cde211a44de5408a9872847fc4cf5348
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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