tert-butyl ((4aR,11bR)-10-(5-chloro-3-vinylpicolinamido)-3,3,11b-trimethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate → tert-butyl ((4aR,11bR)-10-(5-chloro-3-ethylpicolinamido)-3,3,11b-trimethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate

HRID 627753Notes

Reaction equation

HRID 627753 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:39]=[CH2:40])[C:5]([C:8]([NH:10][C:11]2[CH:12]=[CH:13][C:14]3[O:36][CH2:35][CH2:34][C@H:17]4[S:18](=[O:33])(=[O:32])[C:19]([CH3:31])([CH3:30])[C:20]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[N:21][C@:16]4([CH3:37])[C:15]=3[CH:38]=2)=[O:9])=[N:6][CH:7]=1.[H][H]>C(Cl)Cl.[Pd]>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:39][CH3:40])[C:5]([C:8]([NH:10][C:11]2[CH:12]=[CH:13][C:14]3[O:36][CH2:35][CH2:34][C@H:17]4[S:18](=[O:32])(=[O:33])[C:19]([CH3:31])([CH3:30])[C:20]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[N:21][C@:16]4([CH3:37])[C:15]=3[CH:38]=2)=[O:9])=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 131735338tert-butyl ((4aR,11bR)-10-(5-chloro-3-vinylpicolinamido)-3,3,11b-trimethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamateHCID 178418361HCID 178418361, compound

Product 1

HCID 131735339tert-butyl ((4aR,11bR)-10-(5-chloro-3-ethylpicolinamido)-3,3,11b-trimethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of tert-butyl ((4aR,11bR)-10-(5-chloro-3-vinylpicolinamido)-3,3,11b-trimethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate (0.11 g, 0.19 mmol) and palladium, 10% wt. on activated carbon (0.060 g, 0.056 mmol) in DCM (1.0 ml) was stirred under a balloon of hydrogen at room temperature for 12 h. The reaction mixture was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 10% to 60% EtOAc in hexane, to provide tert-butyl ((4aR,11bR)-10-(5-chloro-3-ethylpicolinamido)-3,3,11b-trimethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-2-yl)carbamate as white solid. To a solution of this compound in 1 mL of DCM was added trifluoroacetic acid (0.56 ml, 7.47 mmol). The mixture was stirred at room temperature for 30 min. The solvent was evaporated and the residue was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 0% to 5% MeOH in DCM to give N-((4aR,11bR)-2-amino-3,3,11b-trimethyl-4,4-dioxido-4a,5,6,11b-tetrahydro-3H-benzo[6,7]oxepino[4,5-b][1,4]thiazin-10-yl)-5-chloro-3-ethylpicolinamide (0.010 g, 0.020 mmol, 10.9% yield) as an off-white solid. m/z (ESI) 491.0 (M+H)+.

Workup

  1. customThe reaction mixture was absorbed onto a plug of silica gel
  2. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (12 g)
  3. washeluting with a gradient of 10% to 60% EtOAc in hexane

Sources & evidence

ORD record
ord-148183cc9255486b801cca30440c5370
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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