Piperidine → 1-(5-Cyano-2-pyridinyl)-4-piperidinecarboxylic acid

HRID 2191131Notes

Reaction equation

HRID 2191131 reaction equation
ClC1C=CC([C@@H]2[C@@H]([C@@H](OC3C=CC(Cl)=C(Cl)C=3)C)CCN([C:25]([CH:27]3[CH2:32][CH2:31][N:30]([C:33]4[CH:38]=[CH:37][C:36]([C:39]#[N:40])=[CH:35][N:34]=4)[CH2:29][CH2:28]3)=[O:26])C2)=CC=1.N1C[CH2:45][CH2:44][CH2:43][CH2:42]1.[CH2:47]([N:54]1[CH2:59]C[C@H]([C@H]([OH:62])C)[C@@H:56]([C:63]2[CH:68]=[CH:67][C:66]([Cl:69])=[CH:65][CH:64]=2)[CH2:55]1)[C:48]1[CH:53]=[CH:52]C=CC=1.[F:70][C:71]1[CH:72]=[C:73]([OH:78])[CH:74]=[CH:75][C:76]=1[F:77].ClC([O:82]C(Cl)=O)C.CCN(C(C)C)C(C)C>CO>[C:39]([C:36]1[CH:37]=[CH:38][C:33]([N:30]2[CH2:31][CH2:32][CH:27]([C:25]([OH:26])=[O:62])[CH2:28][CH2:29]2)=[N:34][CH:35]=1)#[N:40].[Cl:69][C:66]1[CH:67]=[CH:68][C:63]([C@@H:56]2[C@@H:43]([C@@H:44]([O:78][C:73]3[CH:74]=[CH:75][C:76]([F:77])=[C:71]([F:70])[CH:72]=3)[CH3:45])[CH2:42][CH2:59][N:54]([C:47]([CH:48]3[CH2:53][CH2:52][N:30]([C:33]4[CH:38]=[CH:37][C:36]([C:39]#[N:40])=[CH:35][N:34]=4)[CH2:31][CH2:32]3)=[O:82])[CH2:55]2)=[CH:64][CH:65]=1

Participants

9

Reactant 6

HCID 8082PiperidineHCID 759273,4-DifluorophenolHCID 81531DiisopropylethylamineHCID 5213051-Chloroethyl chloroformateHCID 468708894-{(3S,4S)-3-(4-Chloro-phenyl)-4-[(S)-1-(3,4-dichloro-phenoxy)-ethyl]-piperidine-1-carbonyl}-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-carbonitrileHCID 59438191(R)-1-[(3S,4S)-1-Benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-ethanol

Product 2

HCID 162274741-(5-Cyano-2-pyridinyl)-4-piperidinecarboxylic acidHCID 468709794-{(3s,4s)-3-(4-Chloro-phenyl)-4-[(s)-1-(3,4-difluoro-phenoxy)-ethyl]-piperidine-1-carbonyl}-3,4,5,6-tetrahydro-2h-[1,2']bipyridinyl-5'-carbonitrile

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

In analogy to the procedure described for the synthesis of 4-{(3S,4S)-3-(4-Chloro-phenyl)-4-[(S)-1-(3,4-dichloro-phenoxy)-ethyl]-piperidine-1-carbonyl}-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-carbonitrile (example 49) the respective piperidine derivative was prepared from (R)-1-[(3S,4S)-1-Benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-ethanol and 3,4-difluoro-phenol via Mitsunobu reaction and subsequently the benzyl group was cleaved by treatment with 1-chloroethyl-chloroformate, DIPEA and methanol. Coupling with 5′-Cyano-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carboxylic acid (commercially available) yielded the title compound as yellow foam. MS (m/e): 565.4 [(M+H)+].

Sources & evidence

ORD record
ord-babd6d47fd5a400f85596e1d45a853bf
Source dataset
uspto-grants-2012_12
Patent number
US08324248B2

Reaction notes

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