2-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indole → HCID 90341055, compound

HRID 595595Notes

Reaction equation

HRID 595595 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[C:9]2[CH:10]=[C:11](B3OC(C)(C)C(C)(C)O3)[C:12]([N:14]([CH3:19])[S:15]([CH3:18])(=[O:17])=[O:16])=[CH:13][C:8]=2[O:7][C:6]=1[C:29]([O:31][CH3:32])=[O:30])=[O:4].Cl[C:34]1[CH:35]=[CH:36][C:37]2[O:50][CH2:49][N:40]3[C:41]4[CH:42]=[CH:43][CH:44]=[C:45]([F:48])[C:46]=4[CH:47]=[C:39]3[C:38]=2[N:51]=1>O1CCOCC1.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].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>[F:48][C:45]1[C:46]2[CH:47]=[C:39]3[C:38]4[N:51]=[C:34]([C:11]5[C:12]([N:14]([CH3:19])[S:15]([CH3:18])(=[O:16])=[O:17])=[CH:13][C:8]6[O:7][C:6]([C:29]([O:31][CH3:32])=[O:30])=[C:5]([C:3](=[O:4])[NH:2][CH3:1])[C:9]=6[CH:10]=5)[CH:35]=[CH:36][C:37]=4[O:50][CH2:49][N:40]3[C:41]=2[CH:42]=[CH:43][CH:44]=1

Participants

5

Reactant 2

HCID 867283052-chloro-11-fluoro-6H-pyrido[2',3':5,6][1,3]oxazino[3,4-a]indoleHCID 90332400HCID 90332400, compound

Product 1

HCID 90341055HCID 90341055, compoundYield 80.7%

Reagents, catalysts & solvents 2

HCID 86681381HCID 86681381, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of compound methyl 3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-2-carboxylate (700 mg, 1.50 mmol), 2-chloro-11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (536 mg, 1.95 mmol) and K3PO4.3H2O (1.20 g, 4.50 mmol) in 1,4-dioxane (25 mL), Pd2(dba)3/XPhos (50 mg/50 mg) was added under N2 protection. After stirring at 100° C. for 3 h, the reaction mixture was concentrated in vacuo, suspended in water and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by prep-TLC (DCM:MeOH=200:1) to give the product of methyl 5-(11-fluoro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indol-2-yl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-2-carboxylate (700 mg, yield: 80%). 1H-NMR (CDCl3, 400 MHz) δ 9.41 (br s, 1H), 8.79 (s, 1H), 7.74 (s, 1H), 7.55˜7.45 (m, 2H), 7.24˜7.17 (m, 2H), 7.12 (d, J=8.0 Hz, 1H), 6.88˜6.81 (m, 1H), 6.01 (s, 2H), 4.10 (s, 3H), 3.40 (s, 3H), 3.05 (d, J=4.4 Hz, 3H), 2.69 (s, 3H). MS (M+H)+: 579.

Workup

  1. additionwas added under N2 protection
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by prep-TLC (DCM:MeOH=200:1)

Sources & evidence

ORD record
ord-8318110effc94d0f87dcedb81f69c736
Source dataset
uspto-grants-2016_01
Patent number
US09242998B2

Reaction notes

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