2-Amino-2-methyl-3-phenylpropan-1-ol → HCID 11375957, compound

HRID 899467Notes

Reaction equation

HRID 899467 reaction equation
[NH2:1][C:2]([CH3:12])([CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH2:3][OH:4].[Na].Br[CH2:15][C:16]1[CH:17]=[C:18]([CH:31]=[C:32]([N:34]([CH3:39])[S:35]([CH3:38])(=[O:37])=[O:36])[CH:33]=1)[C:19]([NH:21][C@@H:22]([C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1)[CH3:23])=[O:20]>CN(C=O)C.C1COCC1>[NH2:1][C:2]([CH3:12])([CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH2:3][O:4][CH2:15][C:16]1[CH:17]=[C:18]([CH:31]=[C:32]([N:34]([CH3:39])[S:35]([CH3:38])(=[O:37])=[O:36])[CH:33]=1)[C:19]([NH:21][C@@H:22]([C:24]1[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=1)[CH3:23])=[O:20]

Participants

6

Reactant 3

HCID 30489922-Amino-2-methyl-3-phenylpropan-1-olHCID 5360545SodiumHCID 16094314HCID 16094314, compound

Product 1

HCID 11375957HCID 11375957, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-amino-2-methyl-3-phenylpropan-1-ol I (28 mg, 0.17 mmol) in 0.5 nL DMF cooled to 0° C. was added sodium hexamethyldisylazide (0.17 mL, 0.17 mmol, 1 M in THF). The reaction mixture was stirred at 0° C. for 5 min and intermediate III 3-(bromomethyl)-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzamide (25 mg, 0.06 mmol) in 0.5 mL DMF was added dropwise. The reaction mixture was stirred at 0° C. for 0.5 h and purified by preparative HPLC (5%->95% CH3CN in water containing 0.1% TFA, C18 PRO YMC 20×150 mm) to afford 3-[(2-amino-2-methyl-3-phenylpropoxy)methyl]-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzamide. 1H NMR (400 MHz, d4-MeOH) δ 8.87 (d, J=8 Hz, 1H), 7.86-7.80 (m, 2H), 7.66 (s, 1H), 7.45-7.40 (m, 2H), 7.36-7.24 (m, 3H), 7.22-7.16 (m, 2H), 7.10-7.02 (m, 2H), 5.30-5.20 (m, 1H), 4.73-4.64 (m, 2H), 3.44 (A of AB, d, J=10 Hz, 1H), 3.39 (B of AB, d, J=10 Hz, 1H), 3.35 (s, 3H), 3.09 (A of AB, d, J=13.2 Hz, 1H), 2.94 (s, 3H), 2.87 (B of AB, d, J=13.2 Hz, 1H), 1.59 (d, J=7.2 Hz, 3H), 1.25 (s, 3H).

Workup

  1. stirringThe reaction mixture was stirred at 0° C. for 0.5 h
  2. custompurified by preparative HPLC (5%->95% CH3CN in water containing 0.1% TFA

Sources & evidence

ORD record
ord-6581a9320bb84501bedf94eabb8063ab
Source dataset
uspto-grants-2008_04
Patent number
US07354942B2

Reaction notes

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