Sodium borohydride → 3-fluoro-4-(2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)benzenamine

HRID 418628Notes

Reaction equation

HRID 418628 reaction equation
[F:1][C:2]1[CH:30]=[C:29]([N+:31]([O-])=O)[CH:28]=[CH:27][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:14]3[N:15]=[CH:16][N:17]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:18]=3)[S:13][C:6]=12.[BH4-].[Na+]>CO.Cl[Ni]Cl>[F:1][C:2]1[CH:30]=[C:29]([NH2:31])[CH:28]=[CH:27][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:14]3[N:15]=[CH:16][N:17]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:25])([CH3:24])[CH3:26])[CH:18]=3)[S:13][C:6]=12

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 594245697-(2-Fluoro-4-nitrophenoxy)-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)thieno[3,2-b]pyridine

Product 1

HCID 587902083-fluoro-4-(2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)benzenamineYield 100%

Reagents, catalysts & solvents 2

HCID 24385Nickel DichlorideCatalystHCID 887MethanolSolvent

Procedure

To a solution of 7-(2-fluoro-4-nitrophenoxy)-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)thieno[3,2-b]pyridine (103) (WO 2006010264) (400 mg, 0.82 mmol) in MeOH (10 mL) at 0° C. was added NiCl2×6H2O (650 mg, 2.5 eq, 2.73 mmol) and NaBH4 (165 mg, 4 eq, 4.4 mmol). The reaction mixture was allowed to stir for 1 hr, concentrated to dryness and the resultant solid was dissolved in 2 M HCl. This solution was then made basic with concentrated aqueous ammonium hydroxide and extracted with DCM. The DCM extract was dried over anhydrous sodium sulfate, filtered and evaporated to give 3-fluoro-4-(2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)benzenamine (104) (350 mg, 100% yield).

Workup

  1. concentrationconcentrated to dryness
  2. dissolutionthe resultant solid was dissolved in 2 M HCl
  3. extractionextracted with DCM
  4. extractionThe DCM extract
  5. dry with materialwas dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-47c5fae3b72d4313b62711d00cf0b901
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Reaction notes

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