Sodium hydride → HCID 71253630, compound

HRID 1775070Notes

Reaction equation

HRID 1775070 reaction equation
[OH:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[H-].[Na+].Cl[C:18]1[N:23]=[C:22]([C:24]2[C:32]3[C:27](=[CH:28][N:29]=[C:30]([C:33]4[CH:34]=[N:35][N:36]([CH3:38])[CH:37]=4)[CH:31]=3)[N:26]([CH:39]3[CH2:44][CH2:43][CH2:42][CH2:41][O:40]3)[N:25]=2)[CH:21]=[CH:20][CH:19]=1>CN(C=O)C>[CH3:38][N:36]1[CH:37]=[C:33]([C:30]2[CH:31]=[C:32]3[C:24]([C:22]4[N:23]=[C:18]([O:1][C@@H:2]5[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]5)[CH:19]=[CH:20][CH:21]=4)=[N:25][N:26]([CH:39]4[CH2:44][CH2:43][CH2:42][CH2:41][O:40]4)[C:27]3=[CH:28][N:29]=2)[CH:34]=[N:35]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1514398(R)-1-Boc-3-hydroxypiperidineHCID 86676693HCID 86676693, compound

Product 1

HCID 71253630HCID 71253630, compoundYield 28.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

To (R)-tert-butyl 3-hydroxypiperidine-1-carboxylate (61.2 mg, 0.30 mmol) in anhydrous DMF (3 mL) was added sodium hydride (40.5 mg, 1.01 mmol, 60% in mineral oil), and the reaction mixture was stirred at 60° C. under N2 for 1 h. A solution of 3-(6-chloropyridin-2-yl)-5-(1-methyl-1H-pyrazol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine (40.0 mg, 0.10 mmol) in anhydrous DMF (˜1.0 mL) was then added, and the reaction mixture was stirred at 90° C. under N2 for 16 h. The reaction mixture was quenched with aqueous saturated NH4Cl solution and was extracted with ethyl acetate (3×). The combined organic layers were dried over Na2SO4, filtered, and evaporated in vacuo. The crude product was purified using flash chromatography (Si-PPC gradient elution, solvent: 0-60% MeOH/EA) to give (3R)-tert-butyl 3-(6-(5-(1-methyl-1H-pyrazol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yloxy)piperidine-1-carboxylate as a foam (15.8 mg, 27.9%). LC/MS: m/z 560.4 [M+1].

Workup

  1. stirringthe reaction mixture was stirred at 90° C. under N2 for 16 h
  2. customThe reaction mixture was quenched with aqueous saturated NH4Cl solution
  3. extractionwas extracted with ethyl acetate (3×)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe crude product was purified
  8. washflash chromatography (Si-PPC gradient elution, solvent: 0-60% MeOH/EA)

Sources & evidence

ORD record
ord-0ddc12d7bfc745ac9f5e31fdf74bdf83
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

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