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

HRID 2191138Notes

Reaction equation

HRID 2191138 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[C@@H:13]([C@@H:14]([O:16][C:17]3C=CC(Cl)=C(Cl)C=3)[CH3:15])[CH2:12][CH2:11][N:10]([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])[CH2:9]2)=[CH:4][CH:3]=1.N1CCCCC1.C(N1CC[C@H]([C@H]([OH:62])C)[C@@H](C2C=CC(Cl)=CC=2)C1)C1C=CC=CC=1.[F:70][C:71]1[CH:72]=[N:73]C(O)=[N:75][CH:76]=1.ClC(OC(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:1][C:2]1[CH:3]=[CH:4][C:5]([C@@H:8]2[C@@H:13]([C@@H:14]([O:16][C:17]3[N:73]=[CH:72][C:71]([F:70])=[CH:76][N:75]=3)[CH3:15])[CH2:12][CH2:11][N:10]([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])[CH2:9]2)=[CH:6][CH:7]=1

Participants

9

Reactant 6

HCID 8082PiperidineHCID 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]-ethanolHCID 178517767HCID 178517767, compound

Product 2

HCID 162274741-(5-Cyano-2-pyridinyl)-4-piperidinecarboxylic acidHCID 46871061HCID 46871061, compound

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 5-fluoro-pyrimidin-2-ol 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 viscous yellow oil. MS (m/e): 549.4 [(M+H)+].

Sources & evidence

ORD record
ord-5c60f1d3bc34411da86cc5474d05258e
Source dataset
uspto-grants-2012_12
Patent number
US08324248B2

Reaction notes

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