Ethyl Acetate → 5-chloro-N-(((3S,3aS)-1-oxo-7-(2-t-butylaminosulfonylphenyl)-1,3,3a,4-tetrahydrobenzo[b]oxazolo[3,4-d][1,4]oxazin-3-yl)methyl)thiophene-2-carboxamide

HRID 1050222Notes

Reaction equation

HRID 1050222 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:9][CH2:10][C@H:11]2[C@H:19]3[N:14]([C:15]4[CH:23]=[CH:22][C:21](B5OC(C)(C)C(C)(C)O5)=[CH:20][C:16]=4[O:17][CH2:18]3)[C:13](=[O:33])[O:12]2)=[O:8])=[CH:4][CH:3]=1.[C:34]([NH:38][S:39]([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=1Br)(=[O:41])=[O:40])([CH3:37])([CH3:36])[CH3:35].C(=O)([O-])[O-].[Cs+].[Cs+].CC(=O)OCC>O1CCOCC1.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:9][CH2:10][C@H:11]2[C@H:19]3[N:14]([C:15]4[CH:23]=[CH:22][C:21]([C:43]5[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=5[S:39]([NH:38][C:34]([CH3:37])([CH3:36])[CH3:35])(=[O:40])=[O:41])=[CH:20][C:16]=4[O:17][CH2:18]3)[C:13](=[O:33])[O:12]2)=[O:8])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 8857Ethyl Acetate2×HCID 10796Cesium carbonateHCID 48250142-bromo-N-tert-butylbenzenesulfonamideHCID 1317360535-chloro-N-(((3S,3 aS)-1-oxo-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,3a,4-tetrahydrobenzo[b]oxazolo[3,4-d][1,4]oxazin-3-yl)methyl)thiophene-2-carboxamide

Product 1

HCID 1185196015-chloro-N-(((3S,3aS)-1-oxo-7-(2-t-butylaminosulfonylphenyl)-1,3,3a,4-tetrahydrobenzo[b]oxazolo[3,4-d][1,4]oxazin-3-yl)methyl)thiophene-2-carboxamideYield 35.6%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Compound 5-chloro-N-(((3S,3aS)-1-oxo-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,3a,4-tetrahydrobenzo[b]oxazolo[3,4-d][1,4]oxazin-3-yl)methyl)thiophene-2-carboxamide (60 mg, 0.122 mmol) and N-t-butyl-o-bromobenzenesulfonamide (43 mg, 0.147 mmol) were dissolved in a mixed solvent of dioxane (5 ml) and water (0.5 ml). Cesium carbonate (80 mg, 0.245 mmol) was added, and tetrakis (triphenylphosphine) palladium (15 mg, 0.012 mmol) was added under the protection of Ar. The resulting mixture was allowed to react under agitation at 80° C. overnight. TLC (PE/EA=1/1) was employed to monitor the reaction. After the reaction completed, the mixture was filtered under reduced pressure, and the solvent was evaporated. Column chromatography (PE/EA=2/1) afforded off-white solid 25 mg, yield: 35.2%.

Workup

  1. customto react under agitation at 80° C. overnight
  2. customthe reaction
  3. filtrationthe mixture was filtered under reduced pressure
  4. customthe solvent was evaporated

Sources & evidence

ORD record
ord-36c9b5179feb4e2f85e30ef9ee93d1e1
Source dataset
uspto-grants-2016_07
Patent number
US09382265B2

Reaction notes

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