Lithium Hydroxide → 3-[(1-{3-Cyano-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propyl}-3-fluoropiperidin-4-yl)oxy]-5-fluorobenzonitrile

HRID 575506Notes

Reaction equation

HRID 575506 reaction equation
C([O:9][CH:10]1[CH2:15][CH2:14][N:13]([CH2:16][CH:17]([N:21]2[CH:25]=[C:24]([C:26]3[C:27]4[CH:34]=[CH:33][N:32](COCC[Si](C)(C)C)[C:28]=4[N:29]=[CH:30][N:31]=3)[CH:23]=[N:22]2)[CH2:18][C:19]#[N:20])[CH2:12][CH:11]1[F:43])(=O)C1C=CC=CC=1.[OH-].[Li+].[C:46](#[N:48])[CH3:47]>O.C(OCC)(=O)C>[C:19]([CH2:18][CH:17]([N:21]1[CH:25]=[C:24]([C:26]2[C:27]3[CH:34]=[CH:33][NH:32][C:28]=3[N:29]=[CH:30][N:31]=2)[CH:23]=[N:22]1)[CH2:16][N:13]1[CH2:14][CH2:15][CH:10]([O:9][C:15]2[CH:14]=[C:47]([CH:12]=[C:11]([F:43])[CH:10]=2)[C:46]#[N:48])[CH:11]([F:43])[CH2:12]1)#[N:20]

Participants

6

Reactant 3

HCID 3939Lithium HydroxideHCID 6342AcetonitrileHCID 696755291-{3-Cyano-2-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propyl}-3-fluoropiperidin-4-yl benzoate

Product 1

HCID 696749183-[(1-{3-Cyano-2-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propyl}-3-fluoropiperidin-4-yl)oxy]-5-fluorobenzonitrileYield 100%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-{3-cyano-2-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propyl}-3-fluoropiperidin-4-yl benzoate (0.389 g, 0.644 mmol) (diastereomer 2) in acetonitrile (2.0 mL) and water (1.0 mL) was added lithium hydroxide (30.8 mg, 1.29 mmol). The reaction solution was stirred at room temperature overnight. The reaction solution was diluted with ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated to give the desired product (0.322 g, 100%). The product was synthesized from diastereomer 1 using same procedure in 100% yield. LCMS (M+H)+: 500.3.

Workup

  1. extractionThe aqueous layer was extracted with ethyl acetate
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-5cad655a03b249c49f4b985a2cad950c
Source dataset
uspto-grants-2015_05
Patent number
US09034884B2

Reaction notes

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