Hydrochloric Acid → HCID 87055066, compound

HRID 2201589Notes

Reaction equation

HRID 2201589 reaction equation
Br[C:2]1[CH:13]=[CH:12][C:5]2[NH:6]C(=O)O[C:9](=[O:10])[C:4]=2[CH:3]=1.CC[N:16](C(C)C)C(C)C.[F:23][C:24]1[CH:29]=[CH:28][C:27]([C@H:30]([NH2:34])[CH2:31][O:32][CH3:33])=[CH:26][CH:25]=1.Cl.N([O-])=O.[Na+].[F:40][C:41]1[CH:46]=[CH:45][C:44]([C:47]2[O:48][C:49]3[CH:59]=[C:58]([N:60]([CH3:65])[S:61]([CH3:64])(=[O:63])=[O:62])[C:57](B4OC(C)(C)C(C)(C)O4)=[CH:56][C:50]=3[C:51]=2[C:52]([NH:54][CH3:55])=[O:53])=[CH:43][CH:42]=1>O1CCOCC1.O.CCOC(C)=O>[F:40][C:41]1[CH:46]=[CH:45][C:44]([C:47]2[O:48][C:49]3[CH:59]=[C:58]([N:60]([CH3:65])[S:61]([CH3:64])(=[O:63])=[O:62])[C:57]([C:2]4[CH:13]=[CH:12][C:5]5[N:6]=[N:16][N:34]([C@@H:30]([C:27]6[CH:26]=[CH:25][C:24]([F:23])=[CH:29][CH:28]=6)[CH2:31][O:32][CH3:33])[C:9](=[O:10])[C:4]=5[CH:3]=4)=[CH:56][C:50]=3[C:51]=2[C:52]([NH:54][CH3:55])=[O:53])=[CH:43][CH:42]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 2885615-Bromoisatoic AnhydrideHCID 23668193Sodium NitriteHCID 28109352HCID 28109352, compoundHCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide

Product 1

HCID 87055066HCID 87055066, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 6-bromo-1H-benzo[d][1,3]oxazine-2,4-dione (22 mg, 0.09 mmol) in 1 ml dioxane was added DIEA (31 μl) followed by (S)-1-(4-fluorophenyl)-2-methoxyethanamine (15 mg, 0.09 mmol). The mixture was microwaved at 100° C. for 30 min. Then 250 μl 2N HCl (aq.) was added followed by a solution of NaNO2 (12.4 mg in 250 μl water). The mixture was stirred at RT for 1 h. To this mixture, 0.5 mL EtOAc was added and stirred for 5 min. Then, the stirring was stopped and the layers were allowed to separate. The bottom aqueous layer was removed by a pipette and was then 250 μl 1N K3PO4 (aq.) was added. To this mixture was added 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (30 mg, 0.06 mmol) followed by Pd(dtbpf)Cl2 (2 mg). The vial was sealed and microwaved at 80° C. for 2 h. The reaction mixtures were diluted with 0.5 mL H2O and the aq. layers were separated. The organic was diluted with 0.5 mL DMF and filtered. The filtrate was purified using semi-prep HPLC to provide (S)-2-(4-fluorophenyl)-5-(3-(1-(4-fluorophenyl)-2-methoxyethyl)-4-oxo-3,4-dihydrobenzo[d][1,2,3]triazin-6-yl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide. (M+H)+: 674.

Workup

  1. customThe mixture was microwaved at 100° C. for 30 min
  2. stirringstirred for 5 min
  3. customto separate
  4. customThe bottom aqueous layer was removed by a pipette
  5. addition250 μl 1N K3PO4 (aq.) was added
  6. customThe vial was sealed
  7. custommicrowaved at 80° C. for 2 h
  8. customThe reaction mixtures
  9. customthe aq. layers were separated
  10. additionThe organic was diluted with 0.5 mL DMF
  11. filtrationfiltered
  12. customThe filtrate was purified

Sources & evidence

ORD record
ord-61ac886762004413bb81ad11b5bcda11
Source dataset
uspto-grants-2016_06
Patent number
US09364482B2

Reaction notes

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