Pyridine → tert-butyl ((4aRS,11bRS)-10-(5-chloro-3-methylpicolinamido)-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 627600Notes

Reaction equation

HRID 627600 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[O:27][CH2:26][CH2:25][CH: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]([CH3:40])[C:34]([C:37](O)=[O:38])=[N:35][CH:36]=1.N1C=CC=CC=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O.C([O-])(O)=O.[Na+].O>[Cl:30][C:31]1[CH:32]=[C:33]([CH3:40])[C:34]([C:37]([NH:1][C:2]2[CH:3]=[CH:4][C:5]3[O:27][CH2:26][CH2:25][CH: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

9

Reactant 4

HCID 1049PyridineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 223920095-Chloro-3-methylpyridine-2-carboxylic acidHCID 123312787tert-butyl ((4aRS,11bRS)-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 123539697tert-butyl ((4aRS,11bRS)-10-(5-chloro-3-methylpicolinamido)-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 80%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Crude tert-butyl ((4aRS,11bRS)-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 (70 mg, 0.165 mmol) was suspended in DMF (2 ml) and sonicated for 1 min. 5-Chloro-3-methylpyridine-2-carboxylic acid (34.0 mg, 0.198 mmol), pyridine (0.04 ml, 0.496 mmol) and HATU (94 mg, 0.248 mmol) were added and resulting suspension was stirred for 45 min at RT. The mixture was diluted with EtOAc (8 ml) and saturated NaHCO3 solution (3 ml). Water was added to dissolve precipitated solids. The organic layer was separated, washed with water and concentrated, and the resulting concentrate/residue was purified by FC on 12 g RediSep Gold column using 10-80% EtOAc in heptane to afford tert-butyl ((4aRS,11bRS)-10-(5-chloro-3-methylpicolinamido)-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 (76 mg, 0.132 mmol, 80% yield) as white solid.

Workup

  1. customsonicated for 1 min
  2. customresulting suspension
  3. dissolutionto dissolve
  4. customprecipitated solids
  5. customThe organic layer was separated
  6. washwashed with water
  7. concentrationconcentrated
  8. customthe resulting concentrate/residue was purified by FC on 12 g RediSep Gold column

Sources & evidence

ORD record
ord-23d830eec3fb450e989262c7eed43a11
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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