Triethylamine → 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

HRID 627752Notes

Reaction equation

HRID 627752 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[O:27][CH2:26][CH2:25][C@H:8]3[S:9](=[O:24])(=[O:23])[C:10]([CH3:22])([CH3:21])[C:11]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[N:12][C@:7]3([CH3:28])[C:6]=2[CH:29]=1.[Cl:30][C:31]1[CH:32]=[C:33]([CH:40]=[CH2:41])[C:34]([C:37](O)=[O:38])=[N:35][CH:36]=1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[Cl:30][C:31]1[CH:32]=[C:33]([CH:40]=[CH2:41])[C:34]([C:37]([NH:1][C:2]2[CH:3]=[CH:4][C:5]3[O:27][CH2:26][CH2:25][C@H:8]4[S:9](=[O:23])(=[O:24])[C:10]([CH3:22])([CH3:21])[C:11]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[N:12][C@:7]4([CH3:28])[C:6]=3[CH:29]=2)=[O:38])=[N:35][CH:36]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867157955-Chloro-3-vinylpicolinic acidHCID 90307362tert-butyl ((4aR,11bR)-10-amino-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

Product 1

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)carbamateYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl ((4aR,11bR)-10-amino-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 (0.080 g, 0.19 mmol) in DCM (2.0 ml) were added 5-chloro-3-vinylpicolinic acid (0.036 g, 0.20 mmol), triethylamine (0.053 ml, 0.38 mmol) and HATU (0.079 g, 0.21 mmol). The mixture was stirred at room temperature for 2 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-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, 99% yield) as a white solid. m/z (ESI) 589.0 (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-bdefa970cdb1481b98a50812055a5c52
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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