Trifluoroacetic acid → HCID 131735104, compound

HRID 929233Notes

Reaction equation

HRID 929233 reaction equation
CN[C@@H]1CCCC[C@H]1NC.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[N:19]1[NH:20][CH:21]=[C:22]2[CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][C:23]=12.[CH2:34]([N:37]1[C:45]2[C:40](=[N:41][C:42](I)=[C:43]([Cl:46])[CH:44]=2)[N:39]=[C:38]1[O:48][C@@H:49]1[CH2:53][O:52][C@@H:51]2[C@H:54]([O:57][Si:58]([C:61]([CH3:64])([CH3:63])[CH3:62])([CH3:60])[CH3:59])[CH2:55][O:56][C@H:50]12)[CH:35]=[CH2:36].[C:65]([OH:71])([C:67]([F:70])([F:69])[F:68])=[O:66]>O1CCOCC1.[Cu]I.C1C=CC=CC=1.C(O)C.C(Cl)Cl>[F:68][C:67]([F:70])([F:69])[C:65]([OH:71])=[O:66].[CH2:34]([N:37]1[C:45]2[C:40](=[N:41][C:42]([N:20]3[CH:21]=[C:22]4[CH2:26][NH:25][CH2:24][C:23]4=[N:19]3)=[C:43]([Cl:46])[CH:44]=2)[N:39]=[C:38]1[O:48][C@@H:49]1[CH2:53][O:52][C@@H:51]2[C@H:54]([O:57][Si:58]([C:61]([CH3:64])([CH3:63])[CH3:62])([CH3:59])[CH3:60])[CH2:55][O:56][C@H:50]12)[CH:35]=[CH2:36]

Participants

11

Reactant 5

HCID 6422Trifluoroacetic acidHCID 62657Potassium Phosphate, TribasicHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 123197088HCID 123197088, compoundHCID 178451520HCID 178451520, compound

Product 1

HCID 131735104HCID 131735104, compound

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 241BenzeneSolventHCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (1R,2R)—N1,N2-dimethylcyclohexane-1,2-diamine (25 uL, 0.158 mmol), copper (I) iodide (4.0 mg, 0.021 mmol), potassium phosphate tribasic (69.7 mg, 0.328 mmol), tert-butyl 4,6-dihydro-2H-pyrrolo[3,4-c]pyrazole-5-carboxylate (42.7 mg, 0.204 mmol) and [(3R,3aR,6R,6aS)-3-(1-allyl-6-chloro-5-iodo-imidazo[4,5-b]pyridin-2-yl)oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy-tert-butyl-dimethyl-silane (84 mg, 0.145 mmol) in dioxane (1.0 ml) was degassed (3×) and placed under nitrogen before being heated to 100° C. After 6 hours, the reaction mixture was diluted with EtOAc (30 ml), washed with water (20 ml), brine (10 mL), dried over MgSO4, filtered, and evaporated under reduced pressure to give an oil. The oil was purified on preparative silica plates (1×1000 u developed with 1:1 EtOAc/hexanes). The resulting solid (86.4 mg, 0.131 mmol) was dissolved in TFA (1.0 mL) and DCM (1.0 mL) and was stirred at room temperature. After 1 hour, the reaction mixture was evaporated to give an oil, and which was lyophilized from ethanol and benzene to give the title compound as a solid. LC-MS: calculated for C26H35ClN6O4Si 558.22 observed m/e: 559.27 (M+H)+ (Rt 1.15/2 min).

Workup

  1. customwas degassed (3×)
  2. additionthe reaction mixture was diluted with EtOAc (30 ml)
  3. washwashed with water (20 ml), brine (10 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customto give an oil
  8. customThe oil was purified on preparative silica plates (1×1000 u developed with 1:1 EtOAc/hexanes)
  9. waitAfter 1 hour
  10. customthe reaction mixture was evaporated
  11. customto give an oil, and which

Sources & evidence

ORD record
ord-ffe94f5060c34c4ea1a136c6df170d07
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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