Sodium hydride → 4-[6-(5-Chloro-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl)-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid tert-butyl ester

HRID 448590Notes

Reaction equation

HRID 448590 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]2[CH2:8][CH2:9][NH:10][C:5]2=[CH:4][CH:3]=1.[H-].[Na+].[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([O:26][C:27]2[CH:32]=[C:31](Cl)[N:30]=[CH:29][N:28]=2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]>CN(C=O)C.C(OCC)(=O)C>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([O:26][C:27]2[CH:32]=[C:31]([N:10]3[C:5]4[C:6](=[N:7][C:2]([Cl:1])=[CH:3][CH:4]=4)[CH2:8][CH2:9]3)[N:30]=[CH:29][N:28]=2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 208229195-Chloro-2,3-dihydro-1H-pyrrolo[3,2-B]pyridineHCID 21906116tert-Butyl 4-[(6-chloropyrimidin-4-yl)oxy]piperidine-1-carboxylate

Product 1

HCID 498486624-[6-(5-Chloro-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl)-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

20a (36 mg, 0.23 mmol) was dissolved in DMF (1.5 mL) with NaH (60% suspension, 9.6 mg, 0.24 mmol). 3a (75 mg, 0.24 mmol) was added slowly. The mixture was stirred at 90° C. for 8 h then cooled down to room temperature, diluted with ethyl acetate and washed with saturated NaHCO3. The organic layer was isolated, dried, filtered and evaporated. The residue was purified by preparative HPLC to afford 20-1, LCMS 432.1 (MH+). tR=5.21 (Method 5). EC50: 751 nM.

Workup

  1. temperaturethen cooled down to room temperature
  2. washwashed with saturated NaHCO3
  3. customThe organic layer was isolated
  4. customdried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by preparative HPLC
  8. customto afford 20-1, LCMS 432.1 (MH+)

Sources & evidence

ORD record
ord-063a4610cc4648bab02367775f28c84e
Source dataset
uspto-grants-2013_07
Patent number
US08481731B2

Reaction notes

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