Propylamine hydrochloride → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-[(propylamino)methyl]-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one

HRID 505283Notes

Reaction equation

HRID 505283 reaction equation
[F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[CH2:30]Br)[C@H:14]2[CH3:32])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH2:35]([NH2:38])[CH2:36][CH3:37].Cl.CCN(C(C)C)C(C)C>CC#N>[F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[CH2:30][NH:38][CH2:35][CH2:36][CH3:37])[C@H:14]2[CH3:32])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

5

Reactant 3

HCID 11165Propylamine hydrochlorideHCID 81531DiisopropylethylamineHCID 57617862(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(bromomethyl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 24896055(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-[(propylamino)methyl]-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(bromomethyl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one (27 mg, 0.0479 mmol) in MeCN (0.5 mL) was added n—PrNH2.HCl (5.5 mg, 0.0575 mmol) and i—Pr2NEt (20.8 μL, 0.120 mmol). The solution was heated at 80° C. for 16 hours. The reaction was then cooled to room temperature and purified by reverse-phase chromatography (C-18, 10 to 95% MeCN/water with 0.1% TFA). The fractions containing the desired product were lyophilized to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-[(propylamino)methyl]-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one (TFA salt). LCMS=543.1 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 9.72 (s, 2H), 7.90 (s, 1H), 7.76 (s, 2H), 7.72 (d, J=6.9 Hz, 1H), 7.56 (d, J=6.4 Hz, 1H), 7.49 (s, 1H), 5.87 (d, J=7.5 Hz, 1H). 4.98 (d, J=15.3 Hz, 1H), 4.35-4.28 (m, 2H), 4.18 (m, 2H), 3.01 (bs, 2H), 1.75-1.60 (m, 2H), 0.96 (m, 3H), 0.90 (d, J=5.5 Hz, 3H).

Workup

  1. temperatureThe reaction was then cooled to room temperature
  2. custompurified by reverse-phase chromatography (C-18, 10 to 95% MeCN/water with 0.1% TFA)
  3. additionThe fractions containing the desired product

Sources & evidence

ORD record
ord-234e27fdd29644119f7bb0b9d4a1ef60
Source dataset
uspto-grants-2010_08
Patent number
US07781426B2

Reaction notes

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