Trifluoroacetic acid → HCID 90308645, compound

HRID 627746Notes

Reaction equation

HRID 627746 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:10][C:11]2[CH:12]=[CH:13][C:14]3[O:44][CH2:43][CH2:42][C@H:18]4[S:19](=[O:41])(=[O:40])[C:20]([CH3:39])([CH3:38])[C:21]([N:23](C(OC(C)(C)C)=O)C(=O)OC(C)(C)C)=[N:22][C@:17]4([CH3:45])[C:15]=3[CH:16]=2)=[O:9])=[N:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:53][C:54]#[N:55].C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>CCOC(C)=O.O.CN(C=O)C>[NH2:23][C:21]1[C:20]([CH3:39])([CH3:38])[S:19](=[O:40])(=[O:41])[C@@H:18]2[CH2:42][CH2:43][O:44][C:14]3[CH:13]=[CH:12][C:11]([NH:10][C:8](=[O:9])[C:5]4[CH:4]=[CH:3][C:2]([O:1][CH2:53][C:54]#[N:55])=[CH:7][N:6]=4)=[CH:16][C:15]=3[C@@:17]2([CH3:45])[N:22]=1

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 10796Cesium carbonateHCID 11534BromoacetonitrileHCID 516892Sodium BicarbonateHCID 90308648HCID 90308648, compound

Product 1

HCID 90308645HCID 90308645, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A vial was charged with tert-butyl N-[(4aR,11bR)-10-[(5-hydroxypyridine-2-carbonyl)amino]-3,3,11b-trimethyl-4,4-dioxo-5,6-dihydro-4aH-[1]benzoxepino[4,5-b][1,4]thiazin-2-yl]-N-tert-butoxycarbonyl-carbamate (150 mg, 0.233 mmol), cesium carbonate (152 mg, 0.465 mmol) and DMF (1163 μl). To this slurry was added 2-bromoacetonitrile (19.81 μl, 0.244 mmol), and the reaction was stirred at RT for 3 h. Water and EtOAc were added and the layers were separated. The organic portion was dried, filtered and concentrated. The crude material was dissolved in 1 mL DCM, and TFA (358 μl, 4.65 mmol) was added and the reaction was stirred for 1 h. EtOAc and saturated NaHCO3 were added, and the layers were separated. The organic portion was dried, filtered and concentrated. The crude product was purified by silica gel chromatography, using a gradient 0-50% 90/10 DCM/MeOH in DCM. The product was further purified by reverse phase chromatography on the Isolera using 0-75% 0.1% TFA/ACN in water solvent system followed by isolation using an SCX column 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-(cyanomethoxy)picolinamide. MS m/z=484.1 (M+H).

Workup

  1. customthe layers were separated
  2. customThe organic portion was dried
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe crude material was dissolved in 1 mL DCM
  6. stirringthe reaction was stirred for 1 h
  7. customthe layers were separated
  8. customThe organic portion was dried
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude product was purified by silica gel chromatography
  12. customThe product was further purified by reverse phase chromatography on the Isolera

Sources & evidence

ORD record
ord-4cbecede65ac45b89b18cb3422201017
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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