1-Hydroxybenzotriazole → 2-[[(2S)-1-[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]-piperidin-2-yl]-methoxy]-1-[4-(2-pyrrolidin-1-yl-ethoxy)-4-[3-(trifluoromethyl)phenyl]-piperidin-1-yl]-ethanone

HRID 1881694Notes

Reaction equation

HRID 1881694 reaction equation
C(N(C(C)C)CC)(C)C.CCN=C=NCCCN(C)C.Cl.Cl.C1C=CC2N(O)N=NC=2C=1.[CH3:33][O:34][C:35]1[CH:40]=[C:39]([CH3:41])[C:38]([S:42]([N:45]2[CH2:50][CH2:49][CH2:48][CH2:47][C@H:46]2[CH2:51][O:52][CH2:53][C:54]([OH:56])=O)(=[O:44])=[O:43])=[C:37]([CH3:57])[CH:36]=1.[N:58]1([CH2:63][CH2:64][O:65][C:66]2([C:72]3[CH:77]=[CH:76][CH:75]=[C:74]([C:78]([F:81])([F:80])[F:79])[CH:73]=3)[CH2:71][CH2:70][NH:69][CH2:68][CH2:67]2)[CH2:62][CH2:61][CH2:60][CH2:59]1>C(Cl)Cl>[CH3:33][O:34][C:35]1[CH:36]=[C:37]([CH3:57])[C:38]([S:42]([N:45]2[CH2:50][CH2:49][CH2:48][CH2:47][C@H:46]2[CH2:51][O:52][CH2:53][C:54]([N:69]2[CH2:70][CH2:71][C:66]([O:65][CH2:64][CH2:63][N:58]3[CH2:62][CH2:61][CH2:60][CH2:59]3)([C:72]3[CH:77]=[CH:76][CH:75]=[C:74]([C:78]([F:80])([F:79])[F:81])[CH:73]=3)[CH2:67][CH2:68]2)=[O:56])(=[O:43])=[O:44])=[C:39]([CH3:41])[CH:40]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531Diisopropylethylamine2×HCID 221413011-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride hydrochlorideHCID 57819715(S)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acidHCID 579162754-(2-(Pyrrolidin-1-yl)ethoxy)-4-(3-(trifluoromethyl)phenyl)piperidine

Product 1

HCID 444656402-[[(2S)-1-[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]-piperidin-2-yl]-methoxy]-1-[4-(2-pyrrolidin-1-yl-ethoxy)-4-[3-(trifluoromethyl)phenyl]-piperidin-1-yl]-ethanoneYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

Diisopropylethylamine (4 eq.), EDCl HCl (1.2 eq.) and HOBt (1 eq.) were added to a mixture of (S)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acid [acid D] (0.65 mmol) in methylene chloride (10 ml). A mixture of 4-(2-(pyrrolidin-1-yl)ethoxy)-4-(3-(trifluoromethyl)phenyl)piperidine [amine H] and DIPEA (2 eq.) in methylene chloride (3 ml) was added dropwise, while cooling with ice, and the reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with methylene chloride, washed with saturated ammonium chloride solution, saturated sodium chloride solution, saturated sodium bicarbonate solution and with sat. sodium chloride solution, dried over sodium sulfate and concentrated. The crude product was purified by means of column chromatography (silica gel, methanol/methylene chloride) to obtain the desired product. Yield: 78%. MS, Rt=3.9 min, m/z=696.4 [MH]+

Workup

  1. additionwas added dropwise
  2. temperaturewhile cooling with ice
  3. washwashed with saturated ammonium chloride solution, saturated sodium chloride solution, saturated sodium bicarbonate solution and with sat. sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe crude product was purified by means of column chromatography (silica gel, methanol/methylene chloride)

Sources & evidence

ORD record
ord-90e61eb30af2456bacc174a8bbc43791
Source dataset
uspto-grants-2012_11
Patent number
US08318769B2

Reaction notes

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