Sodium hydride → HCID 66584846, compound

HRID 2369013Notes

Reaction equation

HRID 2369013 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]1[CH:13]=[N:14][N:15]3[C:20]([NH2:21])=[CH:19][C:18]([CH:22]([NH:24][CH:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)[CH3:23])=[N:17][C:16]=13)=[CH:5]2.[H-].[Na+].Br[CH2:34][CH2:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37]>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]1[CH:13]=[N:14][N:15]3[C:20]([NH:21][CH2:34][CH2:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])=[CH:19][C:18]([CH:22]([NH:24][CH:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)[CH3:23])=[N:17][C:16]=13)=[CH:5]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 256128tert-Butyl 3-bromopropionateHCID 66584734HCID 66584734, compound

Product 1

HCID 66584846HCID 66584846, compoundYield 69.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred solution of 3-(6-fluoroquinolin-3-yl)-5-[1-(tetrahydro-2H-pyran-4-ylamino)ethyl]pyrazolo[1,5-a]pyrimidin-7-amine (240 mg, 0.50 mmol) in anhydrous DMF (6 mL) was treated with sodium hydride (60% suspension in mineral oil, 59 mg, 1.5 mmol) in a single portion under an atmosphere of nitrogen. The resulting yellow-orange slurry was stirred at room temperature for 15 min, and tert-butyl 3-bromopropanoate (128 uL, 0.77 mmol) was added dropwise, gas evolution occurring during the addition. The mixture was stirred at room temperature overnight and was then quenched with water (15 mL) and extracted with EtOAc (2×25 mL). The combined organics were washed with water (3×20 mL) and brine (10 mL), dried over MgSO4, filtered, and concentrated in vacuo and the residue was purified by flash chromatography (40 g silica gel, 3-9% MeOH/DCM) to give tert-butyl 3-(3-(6-fluoroquinolin-3-yl)-5-(1-(tetrahydro-2H-pyran-4-ylamino)ethyl)pyrazolo[1,5-a]pyrimidin-7-ylamino)propanoate (185 mg, 69%) as a glassy solid. MS (ESI+) for C29H35FN6O3 m/z 535 (M+H)+; HPLC, 3.27 min (Method B).

Workup

  1. additiongas evolution occurring during the addition
  2. stirringThe mixture was stirred at room temperature overnight
  3. customwas then quenched with water (15 mL)
  4. extractionextracted with EtOAc (2×25 mL)
  5. washThe combined organics were washed with water (3×20 mL) and brine (10 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customthe residue was purified by flash chromatography (40 g silica gel, 3-9% MeOH/DCM)

Sources & evidence

ORD record
ord-6b02a32ffb1c43aebfbd4d811a08eabf
Source dataset
uspto-grants-2014_04
Patent number
US08703784B2

Reaction notes

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