Water → 5-([1,1'-biphenyl]-4-yl)-6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-2-amine

HRID 929156Notes

Reaction equation

HRID 929156 reaction equation
C1CCN2C(=[N:5]CCC2)CC1.[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]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[C:21]3=[CH:20][C:19]=2[Cl:39])=[CH:14][CH:13]=1.C([O-])(=O)C.[NH4+].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]([NH2:5])[N:26]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[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 517165Ammonium AcetateHCID 682826082-[[6-Chloro-2-methylsulfonyl-5-(4-phenylphenyl)imidazo[4,5-b]pyridin-1-yl]methoxy]ethyl-trimethyl-silane

Product 1

HCID 900418035-([1,1'-biphenyl]-4-yl)-6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-2-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

DBU (0.204 ml, 1.354 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 (232 mg, 0.451 mmol) and ammonium acetate (348 mg, 4.51 mmol) in DMF (2 ml), and the mixture was stirred at room temperature overnight. Water (30 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 HPLC Reverse phase (C-18), eluting with acetonitrile/water+0.1% TFA. The combined fractions was concentrated, dissolved in MeOH, neutralized with NH4OH, concentrated, redissolved in MeOH, filtered through silica gel pad, washed with DCM:MeOH:NH4OH(10:1:0.1) and dried to give title compound. LC-MS: calculated for C24H27ClN4OSi 450.16 observed m/e: 451.13 (M+H)+ (Rt 1.25/2 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 HPLC Reverse phase (C-18)
  7. washeluting with acetonitrile/water+0.1% TFA
  8. concentrationThe combined fractions was concentrated
  9. dissolutiondissolved in MeOH
  10. concentrationconcentrated
  11. dissolutionredissolved in MeOH
  12. filtrationfiltered through silica gel pad
  13. washwashed with DCM:MeOH:NH4OH(10:1:0.1)
  14. customdried

Sources & evidence

ORD record
ord-cbf3311dfbc341dbb8278dbf4627c064
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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