Tetrahydrofuran → HCID 90067260, compound

HRID 929235Notes

Reaction equation

HRID 929235 reaction equation
C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[BH4-].[Na+].C([N:35]1[C:43]2[C:38](=[N:39][C:40]([N:45]3[CH:49]=[C:48]4[CH2:50][N:51]([S:53]([CH3:56])(=[O:55])=[O:54])[CH2:52][C:47]4=[N:46]3)=[C:41]([Cl:44])[CH:42]=2)[N:37]=[C:36]1[O:57][C@@H:58]1[CH2:62][O:61][C@@H:60]2[C@H:63]([O:66][Si](C(C)(C)C)(C)C)[CH2:64][O:65][C@H:59]12)C=C.C1COCC1>C(O)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:44][C:41]1[CH:42]=[C:43]2[NH:35][C:36]([O:57][C@H:58]3[C@H:59]4[O:65][CH2:64][C@@H:63]([OH:66])[C@H:60]4[O:61][CH2:62]3)=[N:37][C:38]2=[N:39][C:40]=1[N:45]1[CH:49]=[C:48]2[CH2:50][N:51]([S:53]([CH3:56])(=[O:55])=[O:54])[CH2:52][C:47]2=[N:46]1

Participants

9

Reactant 4

HCID 8028TetrahydrofuranHCID 812191,3-Bis(diphenylphosphino)propaneHCID 4311764Sodium borohydrideHCID 131735106HCID 131735106, compound

Product 1

HCID 90067260HCID 90067260, compound

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolvent2×HCID 8857Ethyl AcetateSolventHCID 2724141Tetrabutylammonium FluorideSolvent

Procedure

A mixture of palladium acetate (2.5 mg, 0.011 mmol) and DPPP (1.6 mg, 0.0039 mmol) in ethanol (0.1 mL) was stirred for 20 minutes under nitrogen. The resulting dark suspension was added to a mixture of sodium borohydride (18 mg, 0.476 mmol) and [(3R,3aR,6R,6aS)-3-[1-allyl-6-chloro-5-(5-methylsulfonyl-4,6-dihydropyrrolo[3,4-c]pyrazol-2-yl)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 (50.6 mg, 0.079 mmol) in ethanol (0.9 ml). The reaction was stirred at room temperature under a nitrogen atmosphere for 2.5 hours. The reaction mixture was then purified directly on preparative silica plates (1×1000 u developed with 5% MeOH/DCM). The resulting solid was dissolved in 1M TBAF in THF (0.1 mL, 0.1 mmol) and stirred at room temperature for 1 hour. The mixture was diluted with ethyl acetate (20 mL) and washed with water (10 mL). The organic layer was washed with brine (1×5 mL), dried with MgSO4, filtered and the solvent was removed under vacuum. The resulting solid was dissolved in methanol (1.0 mL) and purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting with a 20%-80% acetonitrile/water+0.05% TFA gradient. The desired fractions were lyophilized to give the title compound as a solid. LC-MS: calculated for C1-8H19ClN6O6S 482.08 observed m/e: 483.12 (M+H)+ (Rt 0.97/2 min); 1H NMR δ (ppm) (CD3OD): 7.92 (s, 1H), 7.86 (s, 1H), 5.56 (m, 1H), 4.61 (s, 4H), 4.47 (dd, 1H), 4.29 (m, 1H), 4.18-4.10 (m, 2H), 3.90 (dd, 1H), 3.60 (dd, 1H) and 3.02 (s, 3H).

Workup

  1. stirringThe reaction was stirred at room temperature under a nitrogen atmosphere for 2.5 hours
  2. customThe reaction mixture was then purified directly on preparative silica plates (1×1000 u developed with 5% MeOH/DCM)
  3. stirringstirred at room temperature for 1 hour
  4. washwashed with water (10 mL)
  5. washThe organic layer was washed with brine (1×5 mL)
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. customthe solvent was removed under vacuum
  9. dissolutionThe resulting solid was dissolved in methanol (1.0 mL)
  10. custompurified by preparative HPLC reverse phase (C-18)
  11. washeluting with a 20%-80% acetonitrile/water+0.05% TFA gradient

Sources & evidence

ORD record
ord-09ead5e9a7ae4140a486e7a485c774e2
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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