Sodium → HCID 58856333, compound

HRID 899468Notes

Reaction equation

HRID 899468 reaction equation
[NH2:1][C:2]([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([CH2:5][CH2:6][CH2:7][CH3:8])[CH2:3][OH:4].[Na].Br[CH2:18][C:19]1[CH:20]=[C:21]([CH:34]=[C:35]([N:37]([CH3:42])[S:38]([CH3:41])(=[O:40])=[O:39])[CH:36]=1)[C:22]([NH:24][C@@H:25]([C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=1)[CH3:26])=[O:23]>CN(C=O)C.C1COCC1>[NH2:1][C:2]([CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)([CH2:5][CH2:6][CH2:7][CH3:8])[CH2:3][O:4][CH2:18][C:19]1[CH:20]=[C:21]([CH:34]=[C:35]([N:37]([CH3:42])[S:38]([CH3:41])(=[O:40])=[O:39])[CH:36]=1)[C:22]([NH:24][C@@H:25]([C:27]1[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=1)[CH3:26])=[O:23]

Participants

6

Reactant 3

HCID 5360545SodiumHCID 16094314HCID 16094314, compoundHCID 58856331β-Amino-β-butylbenzenepropanol2×

Product 1

HCID 58856333HCID 58856333, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-amino-2-benzylhexane-1-ol intermediate II (0.100 mg, 0.48 mmol) in 1.1 mL DMF cooled to 0° C. was added sodium hexamethyldisylazide (0.48 mL, 0.48 mmol, 1 M in THF). The reaction mixture was stirred at 0° C. for 5 min and intermediate A 3-(bromomethyl)-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzamide (0.040 g, 0.090 mmol) in 1.8 mL DMF was added dropwise. The reaction mixture was stirred at 0° C. for 1.5 h, and quenched by adding water. The aqueous layer was washed with EtOAc (3×), and the combined organics were washed with brine, dried over Na2SO4, filtered and concentrated. Purification by silica gel chromatography (20 g silica, 0->8% 0.1% NH4OH in i-PrOH/hexanes) afforded 3-{[(2-amino-2-benzylhexyl)oxy]methyl}-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[methyl(methyl sulfonyl)amino]benzamide. 1H NMR (400 MHz, CDCl3) δ 7.73 (s, 1H), 7.69 (s, 1H), 7.53 (s, 1H), 7.37-7.34 (m, 2H), 7.29-7.20 (m, 3H), 7.17-7.15 (m, 2H), 7.04 (m, 2H), 6.56 (br s, 1H), 5.30 (m, 1H), 4.56 (s, 2H), 3.34 (s, 3H), 3.20 (m, 2H), 1.59 (d, J=6.9 Hz, 3H), 1.60-1.39 (br m, 6H), 0.90 (t, J=7.0 Hz, 3H).

Workup

  1. stirringThe reaction mixture was stirred at 0° C. for 1.5 h
  2. customquenched
  3. additionby adding water
  4. washThe aqueous layer was washed with EtOAc (3×)
  5. washthe combined organics were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by silica gel chromatography (20 g silica, 0->8% 0.1% NH4OH in i-PrOH/hexanes)

Sources & evidence

ORD record
ord-84611e3f2d2a4d9fb371808ba61de0fe
Source dataset
uspto-grants-2008_04
Patent number
US07354942B2

Reaction notes

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