Benzyl Alcohol → HCID 178464366, compound

HRID 1399519Notes

Reaction equation

HRID 1399519 reaction equation
[F:1][C:2]([F:55])([F:54])[C:3]1[CH:4]=[C:5]([CH:13]([N:15]([CH2:29][C:30]2[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=2[N:40]([CH2:43][C@H:44]2[CH2:49][CH2:48][C@H:47]([CH2:50][C:51]([OH:53])=[O:52])[CH2:46][CH2:45]2)[CH2:41][CH3:42])[C:16]2[N:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][S:25]([CH3:28])(=[O:27])=[O:26])=[CH:18][N:17]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH2:56](O)[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1.CCN=C=NCCCN(C)C.Cl.O>ClCCl.CN(C1C=CN=CC=1)C>[CH2:56]([O:52][C:51](=[O:53])[CH2:50][C@H:47]1[CH2:48][CH2:49][C@H:44]([CH2:43][N:40]([C:31]2[CH:32]=[CH:33][C:34]([C:36]([F:39])([F:37])[F:38])=[CH:35][C:30]=2[CH2:29][N:15]([CH:13]([C:5]2[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=[C:3]([C:2]([F:1])([F:54])[F:55])[CH:4]=2)[CH3:14])[C:16]2[N:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][S:25]([CH3:28])(=[O:26])=[O:27])=[CH:18][N:17]=2)[CH2:41][CH3:42])[CH2:45][CH2:46]1)[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1

Participants

7

Reactant 4

HCID 244Benzyl AlcoholHCID 962WaterHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178464362HCID 178464362, compound2×

Product 1

HCID 178464366HCID 178464366, compoundYield 95.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of trans-{4-[({2-[({1-[3,5-bis(trifluoromethyl)phenyl]ethyl}{5-[2-(methylsulfonyl)ethoxy]pyrimidin-2-yl}amino)methyl]-4-(trifluoromethyl)phenyl}(ethyl)amino)methyl]cyclohexyl}acetic acid (racemate compound (I), 20 g, 24.61 mmol) synthesized by the method described in Patent document 2 (International Patent Publication WO2008/129951), Example 45 in anhydrous dichloromethane (200 mL) was added with benzyl alcohol (2.93 g, 27.07 mmol), DMAP (300 mg, 2.46 mmol) and WSC.HCl (5.19 g, 27.07 mmol) under ice cooling, and the mixture was warmed to room temperature, and stirred for 16 hours. The reaction mixture was added with water (100 mL), and the mixture was extracted with chloroform (500 mL). The organic layer was washed with 2 M aqueous hydrochloric acid (100 mL) and saturated brine (100 mL), dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure, and the resulting residue was purified by column chromatography (silica gel: 350 g, developing solvent: N-hexane/ethyl acetate=3/1→1/1) to obtain trans-{4-[({2-[({1-[3,5-bis(trifluoromethyl)phenyl]ethyl}{5-[2-(methylsulfonyl)ethoxy]pyrimidin-2-yl}amino)methyl]-4-(trifluoromethyl)phenyl}(ethyl)amino)methyl]cyclohexyl}acetic acid benzyl ester (21.15 g, yield: 95.2%) as white amorphous.

Workup

  1. extractionthe mixture was extracted with chloroform (500 mL)
  2. washThe organic layer was washed with 2 M aqueous hydrochloric acid (100 mL) and saturated brine (100 mL)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customthe resulting residue was purified by column chromatography (silica gel: 350 g, developing solvent: N-hexane/ethyl acetate=3/1→1/1)

Sources & evidence

ORD record
ord-b890ac52b43448978d2d5c6c665e64ff
Source dataset
uspto-grants-2014_12
Patent number
US08906895B2

Reaction notes

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