Sodium → HCID 11478303, compound

HRID 1677593Notes

Reaction equation

HRID 1677593 reaction equation
[NH2:1][C:2]([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([CH2:5][OH:6])[CH2:3][OH:4].[Na].Br[CH2:16][C:17]1[CH:18]=[C:19]([CH:32]=[C:33]([N:35]([CH3:40])[S:36]([CH3:39])(=[O:38])=[O:37])[CH:34]=1)[C:20]([NH:22][C@@H:23]([C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)[CH3:24])=[O:21]>CN(C=O)C.C1COCC1>[NH2:1][C:2]([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([CH2:3][OH:4])[CH2:5][O:6][CH2:16][C:17]1[CH:18]=[C:19]([CH:32]=[C:33]([N:35]([CH3:40])[S:36]([CH3:39])(=[O:38])=[O:37])[CH:34]=1)[C:20]([NH:22][C@@H:23]([C:25]1[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=1)[CH3:24])=[O:21]

Participants

6

Reactant 3

HCID 5360545SodiumHCID 16094314HCID 16094314, compoundHCID 206450782-Amino-2-benzylpropane-1,3-diol

Product 1

HCID 11478303HCID 11478303, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of intermediate I 2-amino-2-benzylpropane-1,3-diol (0.09 g, 0.50 mmol) in 2 mL DMF cooled to 0° C. was added sodium hexamethyldisylazide (0.5 mL, 0.50 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 (0.1 g, 0.23 mmol) in 1 mL DMF was added dropwise. The reaction mixture was stirred at 0° C. for 0.5 h, quenched with water, extracted with EtOAc, washed with aq LiCl (3×), dried over sodium sulfate, concentrated in vacuo, and purified by flash chromatography (40 g silica, 0->8% (10% NH4OH in MeOH)/CH2Cl2) to afford 3-[(2-amino-2-benzyl-3-hydroxypropoxy)methyl]-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzamide. 1H NMR (400 MHz, d4-MeOH) δ 7.80 (s, 2H), 7.64 (s, 1H), 7.44-7.40 (m, 2H), 7.26-7.20 (m, 5H), 7.07-7.02 (m, 2H), 5.24 (q, J=7.0 Hz, 1H), 4.61 (s, 2H), 3.48 (A of AB, d, J=10.4 Hz, 1H), 3.43 (B of AB, d, J=10.4 Hz, 1H), 3.35 (s, 3H), 2.91 (s, 3H), 2.72 (A of AB, d, J=13.9 Hz, 1H), 2.66 (B of AB, d, J=13.9 Hz, 1H), 1.57 (d, J=7.0 Hz, 3H).

Workup

  1. stirringThe reaction mixture was stirred at 0° C. for 0.5 h
  2. customquenched with water
  3. extractionextracted with EtOAc
  4. washwashed with aq LiCl (3×)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. custompurified by flash chromatography (40 g silica, 0->8% (10% NH4OH in MeOH)/CH2Cl2)

Sources & evidence

ORD record
ord-5c709bef37804d1a93365c1f8ae86197
Source dataset
uspto-grants-2011_08
Patent number
US08008315B2

Reaction notes

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