Sodium Hydroxide → HCID 87263219, compound

HRID 604102Notes

Reaction equation

HRID 604102 reaction equation
[F:1][C:2]([F:51])([F:50])[C:3]1[CH:4]=[C:5]([CH:43]=[C:44]([C:46]([F:49])([F:48])[F:47])[CH:45]=1)[CH2:6][N:7]([CH:23]([C:25]1[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][C:26]=1[N:35]([CH2:39][CH:40]1[CH2:42][CH2:41]1)[CH2:36][CH2:37][CH3:38])[CH3:24])[C:8]1[N:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([O:20]CC)=[O:19])=[CH:10][N:9]=1.[OH-].[Na+]>C(O)C>[F:49][C:46]([F:47])([F:48])[C:44]1[CH:43]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:50])[F:51])[CH:45]=1)[CH2:6][N:7]([CH:23]([C:25]1[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][C:26]=1[N:35]([CH2:39][CH:40]1[CH2:41][CH2:42]1)[CH2:36][CH2:37][CH3:38])[CH3:24])[C:8]1[N:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([OH:20])=[O:19])=[CH:12][N:13]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 87263161HCID 87263161, compound

Product 1

HCID 87263219HCID 87263219, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

1-[2-(Cyclopropylmethyl-propyl-amino)-5-trifluoromethyl-phenyl]-ethanol (500 mg) is dissolved in methylene chloride (5 ml) and thereto is added thionyl chloride (133 μl) under ice-cooling and the mixture is stirred at room temperature for 15 minutes. To the reaction solution are added methylene chloride and a saturated aqueous sodium bicarbonate solution, and the mixture is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue and ethyl 4-[2-(3,5-bis-trifluoromethyl-benzylamino)-pyrimidin-5-yloxy]-butyrate (749 mg) are dissolved in N,N-dimethylformamide (5 ml) and thereto is added sodium hydride (62%) (64 mg) under ice-cooling and the mixture is stirred for 1 hour. Thereto are added water and ethyl acetate, and the mixture is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=9:14:1) to give ethyl 4-[2-((3,5-bis-trifluoromethyl-benzyl)-{1-[2-(cyclopropylmethyl-propyl-amino)-5-trifluoromethyl-phenyl]-ethyl}-amino)-pyrimidin-5-yloxy]-butyrate (144 mg) as a crude product. The resulting ester is dissolved in ethanol (2 ml) and thereto is added a 2N-aqueous sodium hydroxide solution (500 μl) and the mixture is stirred at room temperature for 2 hours and concentrated under reduced pressure. To the residue is added ethyl acetate and a dilute hydrochloric acid and the mixture is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (chloroform:methanol=1:0→24:1) to give 4-[2-((3,5-bis-trifluoromethyl-benzyl)-{1-[2-(cyclopropylmethyl-propyl-amino)-5-trifluoromethyl-phenyl]-ethyl}-amino)-pyrimidin-5-yloxy]-butyric acid (11 mg). MS (m/z): 707 [M+H]+

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionTo the residue is added ethyl acetate
  3. customa dilute hydrochloric acid and the mixture is separated
  4. washthe organic layer is washed with a saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue is purified by silica gel column chromatography (chloroform:methanol=1:0→24:1)

Sources & evidence

ORD record
ord-adb0805bfff14a5580b20206f67ed433
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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