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

HRID 1881695Notes

Reaction equation

HRID 1881695 reaction equation
CCN(C(C)C)C(C)C.[CH3:10][O:11][C:12]1[CH:17]=[C:16]([CH3:18])[C:15]([S:19]([N:22]2[CH2:27][CH2:26][CH2:25][CH2:24][C@H:23]2[CH2:28][O:29][CH2:30][C:31]([OH:33])=O)(=[O:21])=[O:20])=[C:14]([CH3:34])[CH:13]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[N:58]1[CH:63]=[CH:62][CH:61]=[C:60]([C:64]2([O:71][CH2:72][CH2:73][N:74]3[CH2:78][CH2:77][CH2:76][CH2:75]3)[CH2:70][CH2:69][CH2:68][NH:67][CH2:66][CH2:65]2)[CH:59]=1>C(Cl)Cl>[CH3:10][O:11][C:12]1[CH:17]=[C:16]([CH3:18])[C:15]([S:19]([N:22]2[CH2:27][CH2:26][CH2:25][CH2:24][C@H:23]2[CH2:28][O:29][CH2:30][C:31]([N:67]2[CH2:68][CH2:69][CH2:70][C:64]([C:60]3[CH:59]=[N:58][CH:63]=[CH:62][CH:61]=3)([O:71][CH2:72][CH2:73][N:74]3[CH2:78][CH2:77][CH2:76][CH2:75]3)[CH2:65][CH2:66]2)=[O:33])(=[O:21])=[O:20])=[C:14]([CH3:34])[CH:13]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57819715(S)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acidHCID 689924974-(Pyridin-3-yl)-4-(2-(pyrrolidin-1-yl)ethoxy)azepan hydrochloride

Product 1

HCID 579162832-[[(2S)-1-[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]-piperidin-2-yl]-methoxy]-1-[4-pyridin-3-yl-4-(2-pyrrolidin-1-yl-ethoxy)-azepan-1-yl]-ethanoneYield 46%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

DIPEA (2.5 eq.) was added to a cooled solution (0° C.) of (S)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acid [acid D] in methylene chloride (5 ml/mmol), followed by HOBt (1 eq.) and EDCl (1.5 eq.). The reaction mixture was stirred at room temperature for 10 min and cooled to 0° C. and 4-(pyridin-3-yl)-4-(2-(pyrrolidin-1-yl)ethoxy)azepan hydrochloride [amine K] (1.2 eq.) was added. The reaction mixture was then stirred at room temperature for 16 h. In this time, the educts reacted completely (TLC control). The reaction mixture was diluted with methylene chloride (20 ml) 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, 2% methanol in methylene chloride). Yield: 46%. MS, Rt=2.8 min, m/z=643.4 [MH]+

Workup

  1. temperaturecooled to 0° C.
  2. stirringThe reaction mixture was then stirred at room temperature for 16 h
  3. customIn this time, the educts reacted completely (TLC control)
  4. washwashed with saturated ammonium chloride solution, saturated sodium chloride solution, saturated sodium bicarbonate solution and finally with sat. sodium chloride solution again
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. concentrationconcentrated to dryness on a rotary evaporator
  7. customThe crude product was purified by means of column chromatography (silica gel, 2% methanol in methylene chloride)

Sources & evidence

ORD record
ord-a45c72f4b30e4ab294d1e864601237f3
Source dataset
uspto-grants-2012_11
Patent number
US08318769B2

Reaction notes

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