Dimethylformamide → 4-{[6-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-pyrimidin-4-yl]-methyl-amino}-piperidine-1-carboxylic acid tert-butyl ester

HRID 448580Notes

Reaction equation

HRID 448580 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[C:19]([N:21]3[C:29]4[C:24](=[CH:25][C:26]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:27][CH:28]=4)[CH2:23][CH2:22]3)[N:18]=[CH:17][N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:36]N(C=O)C.CI>[Cl-].[Na+].O.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]([C:15]2[CH:20]=[C:19]([N:21]3[C:29]4[C:24](=[CH:25][C:26]([S:30]([CH3:33])(=[O:31])=[O:32])=[CH:27][CH:28]=4)[CH2:23][CH2:22]3)[N:18]=[CH:17][N:16]=2)[CH3:36])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 580741254-[6-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-pyrimidin-4-ylamino]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 581165884-{[6-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-pyrimidin-4-yl]-methyl-amino}-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A mixture of 6b (80 mg, 0.17 mmol), NaH (75 mg, 1.87 mmol) and DMF (1 mL) was stirred at room temperature for 30 minutes. Methyl iodide (0.025 mL, 0.4 mmol) was added and the mixture was heated at 90° C. in a sealed vial for 18 h. After cooling to room temperature, DCM (4 mL) and brine (4 mL) were added. The layers were separated and the aqueous layer was extracted with DCM (3×3 mL). The combined extracts were dried, filtered, evaporated and purified by preparative HPLC to give 16-1, LCMS 488.4 (MH+).

Workup

  1. temperaturethe mixture was heated at 90° C. in a sealed vial for 18 h
  2. temperatureAfter cooling to room temperature
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with DCM (3×3 mL)
  5. customThe combined extracts were dried
  6. filtrationfiltered
  7. customevaporated
  8. custompurified by preparative HPLC
  9. customto give 16-1, LCMS 488.4 (MH+)

Sources & evidence

ORD record
ord-61a6171f7e3e40df87f0c3dd5e0516a0
Source dataset
uspto-grants-2013_07
Patent number
US08481731B2

Reaction notes

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