Boron tribromide → HCID 90308628, compound

HRID 627757Notes

Reaction equation

HRID 627757 reaction equation
[NH2:1][C:2]1[C:7]([CH3:9])([CH3:8])[S:6](=[O:11])(=[O:10])[C@@H:5]2[CH2:12][C@H:13]([CH3:34])[O:14][C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22](=[O:33])[C:23]4[C:28]([CH2:29][O:30]C)=[CH:27][C:26]([Cl:32])=[CH:25][N:24]=4)=[CH:17][C:16]=3[C@@:4]2([CH3:35])[N:3]=1.B(Br)(Br)Br>C(Cl)Cl>[NH2:1][C:2]1[C:7]([CH3:9])([CH3:8])[S:6](=[O:10])(=[O:11])[C@@H:5]2[CH2:12][C@H:13]([CH3:34])[O:14][C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22](=[O:33])[C:23]4[C:28]([CH2:29][OH:30])=[CH:27][C:26]([Cl:32])=[CH:25][N:24]=4)=[CH:17][C:16]=3[C@@:4]2([CH3:35])[N:3]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 121266587HCID 121266587, compound

Product 1

HCID 90308628HCID 90308628, compoundYield 24.66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A round bottom flask was charged with N-((4aR,6S,11bR)-2-amino-3,3,6,11b-tetramethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-10-yl)-5-chloro-3-(methoxymethyl)picolinamide (125 mg, 0.240 mmol) and DCM (2.4 ml), and the solution was cooled to 0° C. under nitrogen. BBr3 (47.6 μl, 0.504 mmol) was added dropwise, and the mixture was allowed to warm to RT. After stirring at RT for 1 h, the reaction was quenched with water and neutralized with saturated aqueous sodium bicarbonate. EtOAc was added, and the layers were separated. The aqueous portion was extracted with additional EtOAc, and the combined organic portions were dried over sodium sulfate, filtered and concentrated. The crude material was purified by silica gel chromatography using a gradient of 0-75% 75/25/2 EtOAc/EtOH/NH4OH in heptane to provide N-((4aR,6S,11bR)-2-amino-3,3,6,11b-tetramethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-10-yl)-5-chloro-3-(hydroxymethyl)picolinamide (30 mg, 0.059 mmol, 24.66% yield) as a tan solid. LC/MS (ESI+) m/z=507.0 (M+H).

Workup

  1. temperatureto warm to RT
  2. customthe reaction was quenched with water and neutralized with saturated aqueous sodium bicarbonate
  3. additionEtOAc was added
  4. customthe layers were separated
  5. extractionThe aqueous portion was extracted with additional EtOAc
  6. dry with materialthe combined organic portions were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified by silica gel chromatography

Sources & evidence

ORD record
ord-4ac5807133e84d59930334f011fd2532
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

Loading…