Trimethylsilyl iodide → HCID 58010167, compound

HRID 1854326Notes

Reaction equation

HRID 1854326 reaction equation
[S:1]([N:11]1[C:15]2[N:16]=[CH:17][C:18]3[N:19]([C:20]([C@@H:23]4[C@H:28]5[C@H:26]([CH2:27]5)[C@H:25]([NH:29]C(=O)OCC)[CH2:24]4)=[N:21][N:22]=3)[C:14]=2[CH:13]=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C[Si](I)(C)C.C([O-])(O)=O.[Na+]>C(Cl)Cl>[S:1]([N:11]1[C:15]2[N:16]=[CH:17][C:18]3[N:19]([C:20]([C@@H:23]4[C@H:28]5[C@H:26]([CH2:27]5)[C@H:25]([NH2:29])[CH2:24]4)=[N:21][N:22]=3)[C:14]=2[CH:13]=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:2])=[O:3]

Participants

6

Reactant 4

HCID 85247Trimethylsilyl iodide2×HCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58009912HCID 58009912, compound

Product 1

HCID 58010167HCID 58010167, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of ethyl (1S,2R,4S,5R)-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[3.1.0]hexan-2-ylcarbamate (0.16 g, 0.34 mmol, prepared using GG from Preparation #KK.1, A from Preparation #9 with HATU and TEA, C with TEA) in DCM (2.3 mL) was added trimethylsilyl iodide (0.11 mL, 0.75 mmol). After stirring at ambient temperature for about 24 h, additional trimethylsilyl iodide (0.11 mL, 0.75 mmol) was added and the reaction mixture was heated to about 40° C. for about 4 days. The reaction mixture was cooled to ambient temperature, followed by the addition of saturated aqueous NaHCO3 (20 mL). The mixture was stirred for about 5 min and the layers were separated. The aqueous layer was further extracted with DCM (20 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to afford (1S,2R,4S,5R)-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[3.1.0]hexan-2-amine that contained 1 molar equiv DCM (0.17 g, 100%): LC/MS (Table 2, Method a) Rt=1.76 min; MS m/z: 409 (M+H)+.

Workup

  1. customfrom Preparation #KK.1
  2. temperaturethe reaction mixture was heated to about 40° C. for about 4 days
  3. temperatureThe reaction mixture was cooled to ambient temperature
  4. stirringThe mixture was stirred for about 5 min
  5. customthe layers were separated
  6. extractionThe aqueous layer was further extracted with DCM (20 mL)
  7. washThe combined organic layers were washed with brine (20 mL)
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-01ca5e963303493892875c038f6481a0
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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