3-(Bromomethyl)pyridine → HCID 86591862, compound

HRID 1815709Notes

Reaction equation

HRID 1815709 reaction equation
[C:1]([NH:5][C:6](=[O:8])[OH:7])([CH3:4])([CH3:3])[CH3:2].[CH:9]1([S:12]([NH2:15])(=[O:14])=[O:13])[CH2:11][CH2:10]1.[Li]CCCC.Br[CH2:22][C:23]1[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=1.Br.BrCC1C=NC=CC=1.C(=O)(O)[O-].[Na+]>C1COCC1.CCOCC>[N:25]1[CH:26]=[CH:27][CH:28]=[C:23]([CH2:22][C:9]2([S:12]([NH2:15])(=[O:14])=[O:13])[CH2:11][CH2:10]2)[CH:24]=1.[C:1]([NH:5][C:6](=[O:7])[O-:8])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 2459343-(Bromomethyl)pyridine2×HCID 516892Sodium BicarbonateHCID 127070373-(Bromomethyl)pyridine hydrobromideHCID 68821921Cyclopropylsulfonylamine tert-butylcarbamateHCID 178418339Butyllithium

Product 1

HCID 86591862HCID 86591862, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Step 49a) To a solution of cyclopropylsulfonylamine tert-butyl carbamate (105 g, 4.52 mmol) in THF (9 mL) cooled to −78° C., was added n-BuLi (6.2 mL, 9.2 mmol, 1.6 M in hexane). The mixture was stirred for 1 h at −78° C., and fresh ether solution (2 mL) of 3-(bromomethyl)pyridine was injected in one portion. The fresh 3-(bromomethyl)pyridine was made from 1.5 g (5.9 mmol) of 3-(bromomethyl)pyridine hydrobromide tributed between aqueous sodium bicarbonate and ether. The ether layer was quickly separated, dried (MgSO4), and concentrated in vacuo till about 2 mL liquid left. The reaction mixture was stirred for 4 min, changed the bath into ice water, and stirred for 1 h. The reaction mixture was diluted with pH 4.0 buffer, adjusted pH to 4, and extracted with EtOAc. The extraction was dried (MgSO4), concentrated, and purified by prep-HPLC (sovent B: 0 to 80%) to afford 0.61 g mixture with 1-(3-pyridyl)-cyclopropanesulfonamide-tert-butylcarbamate, and the mixture was used in next step.

Workup

  1. customThe ether layer was quickly separated
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated in vacuo till about 2 mL liquid
  4. waitleft
  5. stirringThe reaction mixture was stirred for 4 min
  6. stirringstirred for 1 h
  7. additionThe reaction mixture was diluted with pH 4.0 buffer
  8. extractionextracted with EtOAc
  9. extractionThe extraction
  10. dry with materialwas dried (MgSO4)
  11. concentrationconcentrated
  12. custompurified by prep-HPLC (sovent B: 0 to 80%)

Sources & evidence

ORD record
ord-460c891e5ad64f14a9123fb04584f809
Source dataset
uspto-grants-2005_04
Patent number
US06878722B2

Reaction notes

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