Methanol → 6-[4-(Benzylamino-methyl)-phenylsulfanyl]-nicotinamide

HRID 2224695Notes

Reaction equation

HRID 2224695 reaction equation
[CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:9]([C:11]1[CH:16]=[CH:15][C:14]([S:17][C:18]2[CH:26]=[CH:25][C:21]([C:22]([NH2:24])=[O:23])=[CH:20][N:19]=2)=[CH:13][CH:12]=1)=O.CO.[BH4-].[Na+]>O>[CH2:1]([NH:8][CH2:9][C:11]1[CH:12]=[CH:13][C:14]([S:17][C:18]2[CH:26]=[CH:25][C:21]([C:22]([NH2:24])=[O:23])=[CH:20][N:19]=2)=[CH:15][CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 7504BenzylamineHCID 4311764Sodium borohydrideHCID 597178526-(4-Formyl-phenylsulfanyl)-nicotinamide

Product 1

HCID 115520286-[4-(Benzylamino-methyl)-phenylsulfanyl]-nicotinamideYield 42.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Combine benzylamine (17 mg, 0.16 mmol), 6-(4-formyl-phenylsulfanyl)-nicotinamide (40 mg, 0.16 mmol), 3 Å molecular sieves (0.1 g), and methanol (3 mL) and stir overnight at room temperature. Filter off the sieves then add sodium borohydride (25 mg, 0.64 mmol) to the reaction and stirred at room temperature for 1 hour. Pour the reaction into water then extract with ethyl acetate (3×10 mL). The combined ethyl acetate extracts were dried over sodium chloride/magnesium sulfate, filtered, and concentrated on a rotary evaporator to yield the crude product (50 mg). The crude product was purified by flash column chromatography on silica gel eluting with 10% aqueous ammonium hydroxide in ethanol and chloroform to yield 6-[4-(benzylamino-methyl)-phenylsulfanyl]-nicotinamide, (24 mg): m/z=349.99(M+1); 1H NMR (MeOD, 300.00 MHz): (8.84 (dd, 1H, J=2.3, 1.0 Hz), 8.02 (dd, 1H, J=8.6, 2.3 Hz), 7.66-7.49 (m, 4H), 7.66-7.49 (m, 4H), 7.42-7.34 (m, 5H), 6.99-6.92 (m, 1H), 3.88-3.77 (m, 4H). HPLC=99% @ 5.82 minutes (5/95 to 95/5 ACN/(0.1% TFA in water) over 10 minutes, Zorbax SB-Phenyl 4.6 mm×15 cm×5 micron, λ=254 nM. By the method of Example 7 the following compounds were prepared, isolated as the free base except where noted:

Workup

  1. filtrationFilter off the sieves
  2. additionPour
  3. extractionthen extract with ethyl acetate (3×10 mL)
  4. dry with materialThe combined ethyl acetate extracts were dried over sodium chloride/magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated on a rotary evaporator
  7. customto yield the crude product (50 mg)
  8. customThe crude product was purified by flash column chromatography on silica gel eluting with 10% aqueous ammonium hydroxide in ethanol and chloroform

Sources & evidence

ORD record
ord-de3d8f8678f14445b50034308e5d51f8
Source dataset
uspto-grants-2008_05
Patent number
US07378448B2

Reaction notes

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