1,4-Bis(diphenylphosphino)butane → HCID 123775948, compound

HRID 929179Notes

Reaction equation

HRID 929179 reaction equation
C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[BH4-].[Na+].C([N:36]1[C:44]2[C:39](=[N:40][C:41]([C:46]3[CH:51]=[CH:50][C:49]([N:52]4[CH2:56][CH2:55][CH2:54][CH2:53]4)=[CH:48][CH:47]=3)=[C:42]([Cl:45])[CH:43]=2)[N:38]=[C:37]1[O:57][C@@H:58]1[CH2:62][O:61][C@@H:60]2[C@H:63]([O:66][Si:67]([C:70]([CH3:73])([CH3:72])[CH3:71])([CH3:69])[CH3:68])[CH2:64][O:65][C@H:59]12)C=C>C(O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:45][C:42]1[CH:43]=[C:44]2[NH:36][C:37]([O:57][C@@H:58]3[CH2:62][O:61][C@@H:60]4[C@H:63]([O:66][Si:67]([C:70]([CH3:73])([CH3:72])[CH3:71])([CH3:68])[CH3:69])[CH2:64][O:65][C@H:59]34)=[N:38][C:39]2=[N:40][C:41]=1[C:46]1[CH:51]=[CH:50][C:49]([N:52]2[CH2:56][CH2:55][CH2:54][CH2:53]2)=[CH:48][CH:47]=1

Participants

6

Reactant 3

HCID 821241,4-Bis(diphenylphosphino)butaneHCID 4311764Sodium borohydrideHCID 90042093HCID 90042093, compound

Product 1

HCID 123775948HCID 123775948, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolvent2×

Procedure

1,4-bis(diphenylphosphino)butane (5.9 mg, 0.014 mmol), palladium(II) acetate (4.0 mg, 0.018 mmol), and ethanol (0.17 ml) were combined in a 4 ml vial. The catalyst mixture was degassed (3×) and placed under nitrogen. The catalyst mixture was an amber suspension that was stirred at room temperature. Sodium borohydride (19.0 mg, 0.502 mmol) was added to a stirred solution of [(3R,3aR,6R,6aS)-3-[1-allyl-6-chloro-5-(4-pyrrolidin-1-ylphenyl)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 (50.3 mg, 0.084 mmol) in ethanol (0.67 ml). The reaction mixture was a yellow suspension that was degassed (3×) and placed under nitrogen. After being stirred at room temperature for 40 minutes, the catalyst mixture was transferred to the reaction mixture via syringe. The reaction mixture was degassed (2×) and placed under nitrogen. After 3.5 hours, the reaction mixture was filtered and evaporated under reduced pressure. The resulting residue was purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting (20 ml/min) with a 14 minute 20%-100% acetonitrile/water+0.05% TFA gradient followed by a 5 minute 100% acetonitrile+0.05% TFA flush. The product fractions were combined, frozen, and lyophilized to give the title compound as a yellow solid. LC-MS: calculated for C28H37ClN4O4Si 556.23 observed m/e: 557.29 (M+H)+ (Rt 1.24/2 min).

Workup

  1. customThe catalyst mixture was degassed (3×)
  2. customwas degassed (3×)
  3. stirringAfter being stirred at room temperature for 40 minutes
  4. customthe catalyst mixture was transferred to the reaction mixture via syringe
  5. customThe reaction mixture was degassed (2×)
  6. filtrationthe reaction mixture was filtered
  7. customevaporated under reduced pressure
  8. customThe resulting residue was purified by preparative HPLC reverse phase (C-18)
  9. washeluting (20 ml/min) with a 14 minute 20%-100% acetonitrile/water+0.05% TFA
  10. waitgradient followed by a 5 minute
  11. custom100% acetonitrile+0.05% TFA flush
  12. temperaturefrozen

Sources & evidence

ORD record
ord-e990982db7814dc8986d3c3531082aae
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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