Trifluoroacetic acid → 2-[[(2S)-1-[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]-piperidin-2-yl]-methoxy]-1-[4-pyridin-4-yl-4-(2-pyrrolidin-1-yl-ethoxy)-piperidin-1-yl]-ethanone

HRID 1881697Notes

Reaction equation

HRID 1881697 reaction equation
CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[CH3:32][O:33][C:34]1[CH:39]=[C:38]([CH3:40])[C:37]([S:41]([N:44]2[CH2:49][CH2:48][CH2:47][CH2:46][C@H:45]2[CH2:50][O:51][CH2:52][C:53]([OH:55])=O)(=[O:43])=[O:42])=[C:36]([CH3:56])[CH:35]=1.[N:57]1[CH:62]=[CH:61][C:60]([C:63]2([O:76][CH2:77][CH2:78][N:79]3[CH2:83][CH2:82][CH2:81][CH2:80]3)[CH2:68][CH2:67][N:66](C(OC(C)(C)C)=O)[CH2:65][CH2:64]2)=[CH:59][CH:58]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:32][O:33][C:34]1[CH:39]=[C:38]([CH3:40])[C:37]([S:41]([N:44]2[CH2:49][CH2:48][CH2:47][CH2:46][C@H:45]2[CH2:50][O:51][CH2:52][C:53]([N:66]2[CH2:67][CH2:68][C:63]([C:60]3[CH:59]=[CH:58][N:57]=[CH:62][CH:61]=3)([O:76][CH2:77][CH2:78][N:79]3[CH2:83][CH2:82][CH2:81][CH2:80]3)[CH2:64][CH2:65]2)=[O:55])(=[O:43])=[O:42])=[C:36]([CH3:56])[CH:35]=1

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 757711-HydroxybenzotriazoleHCID 81531Diisopropylethylamine2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57819715(S)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acidHCID 57916270tert-Butyl 4-(pyridin-4-yl)-4-(2-(pyrrolidin-1-yl)ethoxy)piperidine-1-carboxylate

Product 1

HCID 444658852-[[(2S)-1-[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]-piperidin-2-yl]-methoxy]-1-[4-pyridin-4-yl-4-(2-pyrrolidin-1-yl-ethoxy)-piperidin-1-yl]-ethanoneYield 36%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Procedure

DIPEA (4 eq.), EDCl (1.2 eq.) and HOBt (1 eq.) were added to a solution of (S)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acid [acid D] (0.65 mmol) in methylene chloride (5 ml). tert-Butyl 4-(pyridin-4-yl)-4-(2-(pyrrolidin-1-yl)ethoxy)piperidine-1-carboxylate [amine J] (0.78 mmol) [Boc-deprotected in the presence of TFA (10-13 eq.) in methylene chloride (see e.g. stage (iii)/amine H)] and DIPEA (2 eq.) were added dropwise in methylene chloride (3 ml) to the reaction mixture, while cooling with ice, and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with methylene chloride and washed with saturated ammonium chloride solution, saturated sodium chloride solution, saturated sodium bicarbonate solution and finally with sat. sodium chloride solution again. The organic phase was dried over sodium sulfate and concentrated to dryness on a rotary evaporator. The crude product was purified by means of column chromatography (silica gel, methanol/methylene chloride) to obtain the desired product. Yield: 36%. MS, Rt=2.6 min, m/z=629.4 [MH]+

Workup

  1. temperaturewhile cooling with ice
  2. washwashed with saturated ammonium chloride solution, saturated sodium chloride solution, saturated sodium bicarbonate solution and finally with sat. sodium chloride solution again
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. concentrationconcentrated to dryness on a rotary evaporator
  5. customThe crude product was purified by means of column chromatography (silica gel, methanol/methylene chloride)

Sources & evidence

ORD record
ord-d98153486be0424eac54d4435d023ce8
Source dataset
uspto-grants-2012_11
Patent number
US08318769B2

Reaction notes

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