4-Methylpiperidine → HCID 44479846, compound

HRID 2067971Notes

Reaction equation

HRID 2067971 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH3:13])=[C:11]([C:14]([NH:16][C@H:17]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=3)[CH2:18][CH2:19][CH2:20][C:21]([OH:23])=O)=[O:15])[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[CH3:34][CH:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[CH3:34][CH:35]1[CH2:40][CH2:39][N:38]([C:21](=[O:23])[CH2:20][CH2:19][CH2:18][C@H:17]([NH:16][C:14]([C:11]2[CH:10]=[N:9][N:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)[C:12]=2[CH3:13])=[O:15])[C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:31])([F:32])[F:33])[CH:25]=2)[CH2:37][CH2:36]1

Participants

5

Reactant 3

HCID 693814-MethylpiperidineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 58443409HCID 58443409, compound

Product 1

HCID 44479846HCID 44479846, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (S)-5-{[1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carbonyl]-amino}-5-(3-trifluoromethyl-phenyl)-pentanoic acid (60 mg, 0.13 mmol) and 4-methylpiperidine (40 mg, 0.40 mmol) in DMF (3 mL) is treated with O-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyl-uronium tetrafluoroborate (TBTU) (64 mg, 0.20 mmol). The reaction mixture is stirred at room temperature for 16 hours. The crude reaction mixture is purified directly by preparative reverse phase HPLC (eluted with 10 to 90% CH3CN/H2O and 0.1% TFA as additive) to afford 1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid [(S)-5-(4-methyl-piperidin-1-yl)-5-oxo-1-(3-trifluoromethyl-phenyl)-pentyl]-amide (21 mg, 30% over 2 steps).

Workup

  1. customThe crude reaction mixture
  2. customis purified directly by preparative reverse phase HPLC (eluted with 10 to 90% CH3CN/H2O and 0.1% TFA as additive)

Sources & evidence

ORD record
ord-3ee8aaed6a784547893199a992f3ffd8
Source dataset
uspto-grants-2012_10
Patent number
US08293917B2

Reaction notes

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