Diisopropylethylamine → HCID 58430993, compound

HRID 1040466Notes

Reaction equation

HRID 1040466 reaction equation
[NH:1]1[C:5]2=[N:6][C:7]([C:10]#[N:11])=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2]1.[CH3:12][CH2:13][Mg+].[Br-].[CH3:16][CH2:17]N(C(C)C)C(C)C.[CH3:25][C:26]([O:29][C:30](O[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[O:31])([CH3:28])[CH3:27]>C1COCC1.C(Cl)Cl.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[C:26]([O:29][C:30](=[O:31])[NH:11][C:10]1([C:7]2[N:6]=[C:5]3[NH:1][CH:2]=[CH:3][C:4]3=[CH:9][CH:8]=2)[CH2:13][CH2:12]1)([CH3:28])([CH3:27])[CH3:25].[C:36]([O:35][C:33](=[O:34])[NH:11][CH:10]([C:7]1[N:6]=[C:5]2[NH:1][CH:2]=[CH:3][C:4]2=[CH:9][CH:8]=1)[CH2:16][CH3:17])([CH3:37])([CH3:38])[CH3:39]

Participants

9

Reactant 4

HCID 81531DiisopropylethylamineHCID 90495Di-tert-butyl dicarbonateHCID 105347761H-pyrrolo[2,3-b]pyridine-6-carbonitrileHCID 178461630HCID 178461630, compound

Product 2

HCID 58430993HCID 58430993, compoundHCID 58431253HCID 58431253, compound

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1H-Pyrrolo[2,3-b]pyridine-6-carbonitrile (500 mg, 3.49 mmol) in THF (80 mL) was added Titanium (IV) isopropoxide (2.05 mL, 6.98 mmol) followed by EtMgBr (4.66 mL, 13.97 mmol) dropwise. The mixture was stirred at room temperature for 3 h. The dark color reaction mixture was quenched with 10 mL of H2O and stirred efficiently for 30 min. The resulting yellow suspension was filtered through a plug of celite, washed the celite cake with EtOAc followed by 10% MeOH/CH2Cl2. Solvents were removed and the resulting brown oil was suspended in Toluene (2×10 mL) to removed residual water. After evaporation of the solvent the crude amine products were obtained as a brownish solid. To a mixture of these crude amines and DIEA (801 uL, 4.60 mmol) in DCM (15 mL) was added Boc2O (810 mg, 3.71 mmol). The mixture was stirred at room temperature for 16 h. The reaction was diluted with DCM and washed with water, followed by Brine. Dried over MgSO4, filtered and concentrated down to provide crude material which was purified by silica gel chromatography (5% to 50% EtOAc in hexane) to give 80 mg of [1-(1H-Pyrrolo[2,3-b]pyridin-6-yl)-cyclopropyl]-carbamic acid tert-butyl ester (m/z 274.40 [M+1]+) and 230 mg of [1-(1H-Pyrrolo[2,3-b]pyridin-6-yl)-propyl]-carbamic acid tert-butyl ester m/z 276.41 [M+1]+

Workup

  1. customThe dark color reaction mixture
  2. customwas quenched with 10 mL of H2O
  3. stirringstirred efficiently for 30 min
  4. filtrationThe resulting yellow suspension was filtered through a plug of celite
  5. washwashed the celite cake with EtOAc
  6. customSolvents were removed
  7. customto removed residual water
  8. customAfter evaporation of the solvent the crude amine products
  9. customwere obtained as a brownish solid
  10. stirringThe mixture was stirred at room temperature for 16 h
  11. washwashed with water
  12. dry with materialDried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated down
  15. customto provide crude material which
  16. customwas purified by silica gel chromatography (5% to 50% EtOAc in hexane)

Sources & evidence

ORD record
ord-2a5bf4dc9d2e45ec89d1a71e256d97dd
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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