Water → (3R,3aR,6aR)-6-(2-((5-([1,1'-biphenyl]-4-yl)-6-chloro-1H-imidazo[4,5-b]pyridin-2-yl)oxy)ethyl)hexahydrofuro[3,2-b]furan-3-ol

HRID 929213Notes

Reaction equation

HRID 929213 reaction equation
N1CCCN2CCCCCC=12.[C:12]1([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH:17]=[CH:16][C:15]([C:18]2[N:23]=[C:22]3[N:24]=[C:25](S(C)(=O)=O)[N:26](COCC[Si](C)(C)C)[C:21]3=[CH:20][C:19]=2[Cl:39])=[CH:14][CH:13]=1.[Si]([O:53][C@H:54]1[C@H:58]2[O:59][CH2:60][CH:61]([CH2:62][CH2:63][OH:64])[C@H:57]2[O:56][CH2:55]1)(C(C)(C)C)(C)C.O>CN(C=O)C>[C:12]1([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH:17]=[CH:16][C:15]([C:18]2[N:23]=[C:22]3[N:24]=[C:25]([O:64][CH2:63][CH2:62][CH:61]4[C@H:57]5[O:56][CH2:55][C@@H:54]([OH:53])[C@H:58]5[O:59][CH2:60]4)[NH:26][C:21]3=[CH:20][C:19]=2[Cl:39])=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 962WaterHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 682826082-[[6-Chloro-2-methylsulfonyl-5-(4-phenylphenyl)imidazo[4,5-b]pyridin-1-yl]methoxy]ethyl-trimethyl-silaneHCID 900420242-((3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)hexahydrofuro[3,2-b]furan-3-yl)ethanol

Product 1

HCID 90067536(3R,3aR,6aR)-6-(2-((5-([1,1'-biphenyl]-4-yl)-6-chloro-1H-imidazo[4,5-b]pyridin-2-yl)oxy)ethyl)hexahydrofuro[3,2-b]furan-3-ol

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine (0.019 ml, 0.128 mmol) was added to a stirred mixture of 5-([1,1′-biphenyl]-4-yl)-6-chloro-2-(methylsulfonyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridine (52.6 mg, 0.102 mmol) and 2-((3aR,6R,6aS)-6-((tert-butyldimethylsilyl)-oxy)hexahydro-furo[3,2-b]furan-3-yl)ethanol (38.4 mg, 0.133 mmol) in DMF (1 ml) and the mixture was stirred at room temperature overnight. Water (20 mL) was added and the mixture was extracted with ethyl acetate (2×30 mL). The combined organic fractions were washed with brine (saturated, 20 mL), dried (Na2SO4), filtered and the solvent was evaporated under reduced pressure. The resulting residue was purified by preparative TLC, eluting with EtOAc/isohexane (1:1) to give the title compound. LC-MS: calculated for C38H52ClN3O5Si2 721.31 observed m/e: 722.39 (M+H)+ (Rt 1.58/2 min)

Workup

  1. extractionthe mixture was extracted with ethyl acetate (2×30 mL)
  2. washThe combined organic fractions were washed with brine (saturated, 20 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customthe solvent was evaporated under reduced pressure
  6. customThe resulting residue was purified by preparative TLC
  7. washeluting with EtOAc/isohexane (1:1)

Sources & evidence

ORD record
ord-4a365d753d3842d4a554313552fba4c0
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

Loading…