Sulfuric Acid → 5-([1,1'-biphenyl]-4-yl)-2-(((3R,3aR,6R,6aR)-6-hydroxyhexahydrofuro[3,2-b]furan-3-yl)oxy)-1H-imidazo[4,5-b]pyridine-6-carbonitrile

HRID 929248Notes

Reaction equation

HRID 929248 reaction equation
S(=O)(=O)(O)O.[C:6]1([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH:11]=[CH:10][C:9]([C:12]2[N:17]=[C:16]3[N:18]=[C:19]([O:29][C@H:30]4[C@H:34]5[O:35][CH2:36][C@@H:37]([OH:38])[C@H:33]5[O:32][CH2:31]4)[N:20](COCC[Si](C)(C)C)[C:15]3=[CH:14][C:13]=2Cl)=[CH:8][CH:7]=1.[C:46]([Zn]C#N)#[N:47]>CC(N(C)C)=O.CN(C=O)C.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[C:6]1([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH:7]=[CH:8][C:9]([C:12]2[N:17]=[C:16]3[N:18]=[C:19]([O:29][C@@H:30]4[CH2:31][O:32][C@@H:33]5[C@H:37]([OH:38])[CH2:36][O:35][C@H:34]45)[NH:20][C:15]3=[CH:14][C:13]=2[C:46]#[N:47])=[CH:10][CH:11]=1

Participants

7

Reactant 3

HCID 1118Sulfuric AcidHCID 89558893(3R,3aR,6R,6aR)-6-((5-([1,1'-biphenyl]-4-yl)-6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol2×HCID 178514179HCID 178514179, compound

Product 1

HCID 900674605-([1,1'-biphenyl]-4-yl)-2-(((3R,3aR,6R,6aR)-6-hydroxyhexahydrofuro[3,2-b]furan-3-yl)oxy)-1H-imidazo[4,5-b]pyridine-6-carbonitrile

Reagents, catalysts & solvents 3

HCID 12976736Bis(ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane);iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 31374DimethylacetamideSolvent2×

Conditions

Temperature
80 °C

Procedure

A mixture of PdOAc2 (15.48 mg, 0.069 mmol) and 1,1′-bis(di-tert-butylphoshino)ferrocene (32.7 mg, 0.069 mmol) in DMAc (0.25 ml) was treated with sulfuric acid (6.76 mg, 0.069 mmol) and stirred at 80° C. for 30 min. Then a solution of (3R,3aR,6R,6aR)-6-((5-([1,1′-biphenyl]-4-yl)-6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)hexahydrofuro[3,2-b]furan-3-ol (Intermediate 8, 40 mg, 0.069 mmol) and dicyanozinc (9.71 mg, 0.083 mmol) in DMAc (0.25 ml) was added to the reaction and the reaction was heated to 120 degrees for 16 h. The residue was diluted with 0.7 ml DMF, filtered and purified by mass directed reverse phase column chromatography eluting with acetonitrile/water+0.1% TFA to give the title compound. LC-MS: calculated for C25H20N4O4, 440.15, observed m/e: 441.15 (M+H)+ (RT 0.58/2.00 min).

Workup

  1. temperaturethe reaction was heated to 120 degrees for 16 h
  2. filtrationfiltered
  3. custompurified by mass
  4. washeluting with acetonitrile/water+0.1% TFA

Sources & evidence

ORD record
ord-261154eec9234c74b31c62350ace5d3f
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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