1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperidine-4-carboxylic acid [3-(4-fluoro-phenoxy)-phenyl]-amide → HCID 58694695, compound

HRID 29885Notes

Reaction equation

HRID 29885 reaction equation
[F:1][C:2]1[CH:33]=[CH:32][C:5]([O:6][C:7]2[CH:8]=[C:9]([NH:13][C:14]([CH:16]3[CH2:21][CH2:20][N:19]([C:22]4[C:23]5[C:30]([CH3:31])=[CH:29][NH:28][C:24]=5[N:25]=[CH:26][N:27]=4)[CH2:18][CH2:17]3)=O)[CH:10]=[CH:11][CH:12]=2)=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[F:1][C:2]1[CH:33]=[CH:32][C:5]([O:6][C:7]2[CH:8]=[C:9]([NH:13][CH2:14][CH:16]3[CH2:21][CH2:20][N:19]([C:22]4[C:23]5[C:30]([CH3:31])=[CH:29][NH:28][C:24]=5[N:25]=[CH:26][N:27]=4)[CH2:18][CH2:17]3)[CH:10]=[CH:11][CH:12]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 117192531-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperidine-4-carboxylic acid [3-(4-fluoro-phenoxy)-phenyl]-amideHCID 21226445Aluminium lithium hydride

Product 1

HCID 58694695HCID 58694695, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperidine-4-carboxylic acid [3-(4-fluoro-phenoxy)-phenyl]-amide (52 mg, 0.12 mmol) in anhydrous THF (tetrahydrofuran) (10 mL) was cooled in an ice bath for 15 minutes with stirring. To this a solution of LAH (lithium aluminum hydride) in THF (1.0 M, 1.2 mL, 1.2 mmol) was added slowly. The reaction mixture was warmed to room temperature and stirred for 15 minutes, and then heated to reflux for 2 hours. The mixture was cooled to room temperature and then Na2SO4.10H2O was added until bubbling stopped. After stirring for 2 hours, the precipitate was filtered off and the filtrate concentrated. The residue was dissolved in acetonitrile (1.5 mL) and 30% aqueous TFA (trifluoroacetic acid) (0.5 mL), filtered, and chromatographed using reverse-phase high-pressure liquid chromatography. The clean fractions were pooled and concentrated and then lyophilized to remove water to yield [3-(4-fluoro-phenoxy)-phenyl]-[1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperidin-4-ylmethyl]-amine as a white solid (7.9 mg, 15%, (M+H)+:432).

Workup

  1. stirringstirred for 15 minutes
  2. temperatureheated
  3. temperatureto reflux for 2 hours
  4. temperatureThe mixture was cooled to room temperature
  5. customuntil bubbling
  6. stirringAfter stirring for 2 hours
  7. filtrationthe precipitate was filtered off
  8. concentrationthe filtrate concentrated
  9. dissolutionThe residue was dissolved in acetonitrile (1.5 mL)
  10. filtration30% aqueous TFA (trifluoroacetic acid) (0.5 mL), filtered
  11. customchromatographed
  12. concentrationconcentrated
  13. customto remove water

Sources & evidence

ORD record
ord-7eb321786f8843c3a6f3ba6551048b96
Source dataset
uspto-grants-2008_09
Patent number
US07423043B2

Reaction notes

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