Pyridine → HCID 131731671, compound

HRID 1626290Notes

Reaction equation

HRID 1626290 reaction equation
[F:1][C:2]([F:14])([F:13])[C@@H:3]1[CH2:8][CH2:7][NH:6][CH2:5][C@H:4]1[C:9]([O:11]C)=[O:10].Cl[C:16]1[N:21]=[CH:20][NH:19][C:18]2=[N:22][CH:23]=[CH:24][C:17]=12.N1C=CC=CC=1.[Li+].[OH-]>CN(C=O)C.[Cl-].[Na+].O.O>[N:19]1[C:18]2[NH:22][CH:23]=[CH:24][C:17]=2[C:16]([N:6]2[CH2:7][CH2:8][C@@H:3]([C:2]([F:14])([F:13])[F:1])[C@H:4]([C:9]([OH:11])=[O:10])[CH2:5]2)=[N:21][CH:20]=1

Participants

8

Reactant 4

HCID 1049PyridineHCID 3939Lithium HydroxideHCID 96532006HCID 96532006, compoundHCID 178418725HCID 178418725, compound

Product 1

HCID 131731671HCID 131731671, compoundYield 52.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of racemic trans-methyl 4-(trifluoromethyl)piperidine-3-carboxylate E (1.00 g, 4.74 mmol), 4-chloropyrrolo[2,3-d]pyrimidine (0.873 g, 5.68 mmol) and pyridine (0.766 mL, 9.47 mmol) in DMF (5 mL) was heated at 80° C. for 24 hours. The solution was diluted with brine and the reaction mixture was extracted with EtOAc. The organic phase was concentrated in vacuo to afford a residue which was treated with LiOH (0.9 g, 37.8 mmol) in water (40 mL) was stirred for 68 h. The resulting precipitate was filtered to afford a solid G (782 mg, 52.5% yield). 1H NMR (400 MHz, DMSO-d6) δ=11.63 (br. s., 1 H), 8.11 (s, 1 H), 7.15 (dd, J=2.5, 3.5 Hz, 1 H), 6.60 (dd, J=1.9, 3.6 Hz, 1 H), 4.48 (m, 2 H), 3.46-3.34 (m, 1 H), 3.25-3.12 (m, 1 H), 2.18 (m, 1 H), 1.88 (m, 1 H), 1.51 (m, 1 H); m/z 315 [M+1].

Workup

  1. extractionthe reaction mixture was extracted with EtOAc
  2. concentrationThe organic phase was concentrated in vacuo
  3. customto afford a residue which
  4. filtrationThe resulting precipitate was filtered
  5. customto afford a solid G (782 mg, 52.5% yield)

Sources & evidence

ORD record
ord-ea6844b186ce40e2a8c0bbda31676a30
Source dataset
uspto-grants-2014_07
Patent number
US08785440B2

Reaction notes

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