Hydrochloric Acid → 4-{3-(cyanomethyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-2-fluorobenzoic acid

HRID 2363304Notes

Reaction equation

HRID 2363304 reaction equation
[C:1]([CH2:3][C:4]1([N:19]2[CH:23]=[C:22]([C:24]3[C:25]4[CH:32]=[CH:31][N:30]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[C:26]=4[N:27]=[CH:28][N:29]=3)[CH:21]=[N:20]2)[CH2:7][N:6]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14]C)=[O:13])=[C:10]([F:18])[CH:9]=2)[CH2:5]1)#[N:2].[OH-].[Li+].Cl>O1CCCC1.O>[C:1]([CH2:3][C:4]1([N:19]2[CH:23]=[C:22]([C:24]3[C:25]4[CH:32]=[CH:31][N:30]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:38])([CH3:40])[CH3:39])[C:26]=4[N:27]=[CH:28][N:29]=3)[CH:21]=[N:20]2)[CH2:5][N:6]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([OH:14])=[O:13])=[C:10]([F:18])[CH:9]=2)[CH2:7]1)#[N:2]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 71143590Methyl 4-{3-(Cyanomethyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-2-fluorobenzoate

Product 1

HCID 711436084-{3-(cyanomethyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-2-fluorobenzoic acidYield 77.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
35 °C

Procedure

To a solution of methyl 4-{3-(cyanomethyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-2-fluorobenzoate (1.22 g, 2.17 mmol) in tetrahydrofuran (10 mL) was added a solution of lithium hydroxide (0.21 g, 8.8 mmol) in water (9.8 mL). The reaction mixture was then stirred at 35° C. for 24 hours. The reaction mixture was diluted with water (5 mL) and pH was adjusted to ˜4 with 1 N HCl, extracted with ethyl acetate. The organic fraction was washed with water (1×), brine (1×), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The solid was then triturated with methylene chloride-methanol (95:5), filtrated to afford the desired product (0.917 g, 77.1%). LCMS (M+H)+: m/z=562.2.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic fraction was washed with water (1×), brine (1×)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe solid was then triturated with methylene chloride-methanol (95:5)
  7. filtrationfiltrated

Sources & evidence

ORD record
ord-a7de9e4c946a4a6d91d6ecd962b8e9d8
Source dataset
uspto-grants-2014_04
Patent number
US08691807B2

Reaction notes

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