Sodium borohydride → [2-(2-{3-Amino-2-[bis-(4-methoxybenzyl)amino]-6-chloro-5-methylpyridin-4-ylamino}ethoxy)ethyl]carbamic acid tert-butyl ester

HRID 1008099Notes

Reaction equation

HRID 1008099 reaction equation
[BH4-].[Na+].[C:3]([O:7][C:8](=[O:46])[NH:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][NH:15][C:16]1[C:21]([CH3:22])=[C:20]([Cl:23])[N:19]=[C:18]([N:24]([CH2:34][C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=2)[CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[C:17]=1[N+:43]([O-])=O)([CH3:6])([CH3:5])[CH3:4]>CO.ClCCl.O.[Ni](Cl)Cl>[C:3]([O:7][C:8](=[O:46])[NH:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][NH:15][C:16]1[C:21]([CH3:22])=[C:20]([Cl:23])[N:19]=[C:18]([N:24]([CH2:34][C:35]2[CH:36]=[CH:37][C:38]([O:41][CH3:42])=[CH:39][CH:40]=2)[CH2:25][C:26]2[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=2)[C:17]=1[NH2:43])([CH3:4])([CH3:6])[CH3:5]

Participants

6

Reactant 2

HCID 4311764Sodium borohydrideHCID 86590766{2-[2-(2-[Bis{4-methoxybenzyl}amino]-6-chloro-5-methyl-3-nitropyridin-4-ylamino)ethoxy]ethyl}carbamic acid tert-butyl ester

Product 1

HCID 86590768[2-(2-{3-Amino-2-[bis-(4-methoxybenzyl)amino]-6-chloro-5-methylpyridin-4-ylamino}ethoxy)ethyl]carbamic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 16212333Nickel chloride hydrateCatalystHCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

Under a nitrogen atmosphere, sodium borohydride (0.76 g, 20.0 mmol) was added in two portions to a solution of nickel (II) chloride hydrate (1.57 g, 6.62 mmol) in methanol (160 mL), and the mixture was stirred at room temperature for 15 minutes. A solution of {2-[2-(2-[bis {4-methoxybenzyl}amino]-6-chloro-5-methyl-3-nitropyridin-4-ylamino)ethoxy]ethyl}carbamic acid tert-butyl ester (8.37 g, 13.3 mmol) in methanol (10 mL) and dichloromethane (10 mL) was then added, and the addition funnel was rinsed with a mixture of methanol (10 mL) and dichloromethane (10 mL). The reaction was stirred for two hours, during which time additional sodium borohydride was added three times (0.5 g, 0.5, g and 1.0 g). Water (200 mL) was then added, and the methanol was removed under reduced pressure. The remaining solution was extracted with diethyl ether (700 mL, 300 mL), and the combined extracts were washed with water (200 mL) and brine (200 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to product the crude product contaminated with water. Toluene (300 mL) was added and then removed by distillation to provide [2-(2-{3-amino-2-[bis-(4-methoxybenzyl)amino]-6-chloro-5-methylpyridin-4-ylamino}ethoxy)ethyl]carbamic acid tert-butyl ester, which was used in Part F without further purification.

Workup

  1. washthe addition funnel was rinsed with a mixture of methanol (10 mL) and dichloromethane (10 mL)
  2. stirringThe reaction was stirred for two hours, during which time additional sodium borohydride
  3. additionwas added three times (0.5 g, 0.5, g and 1.0 g)
  4. additionWater (200 mL) was then added
  5. customthe methanol was removed under reduced pressure
  6. extractionThe remaining solution was extracted with diethyl ether (700 mL, 300 mL)
  7. washthe combined extracts were washed with water (200 mL) and brine (200 mL)
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure to product the crude product
  11. additionToluene (300 mL) was added
  12. customremoved by distillation

Sources & evidence

ORD record
ord-86711827ad494a54aafd6c0a5059ce03
Source dataset
uspto-grants-2004_09
Patent number
US06797718B2

Reaction notes

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