Tert-Butylamine → N-tert-butyl-5-iodo-4-(2-(thiophen-3-yl)ethoxy)pyridin-2-amine

HRID 84596

Reaction equation

HRID 84596 reaction equation
C1(C)C=CC(S(OS(C2C=CC(C)=CC=2)(=O)=O)(=O)=O)=CC=1.[I:22][C:23]1[CH:24]=[N+:25]([O-])[CH:26]=[CH:27][C:28]=1[O:29][CH2:30][CH2:31][C:32]1[CH:36]=[CH:35][S:34][CH:33]=1.[C:38]([NH2:42])([CH3:41])([CH3:40])[CH3:39]>C(Cl)(Cl)Cl>[C:38]([NH:42][C:26]1[CH:27]=[C:28]([O:29][CH2:30][CH2:31][C:32]2[CH:36]=[CH:35][S:34][CH:33]=2)[C:23]([I:22])=[CH:24][N:25]=1)([CH3:41])([CH3:40])[CH3:39]

Participants

5

Reactant 3

HCID 6385Tert-Butylamine2×HCID 77773Toluene-p-sulphonic anhydride2×HCID 582840413-Iodo-4-(2-(thiophen-3-yl)ethoxy)pyridine 1-oxide

Product 1

HCID 57900152N-tert-butyl-5-iodo-4-(2-(thiophen-3-yl)ethoxy)pyridin-2-amine

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

A solution of p-toluenesulfonic anhydride (1.47 g, 4.49 mmol) in 15 ml of chloroform was added dropwise to a stirred mixture of 0.78 g (2.25 mmol) of 3-iodo-4-(2-(thiophen-3-yl)ethoxy)pyridine 1-oxide and 1.18 ml (11.2 mmol) of tert-butylamine in 15 ml of chloroform at 0° C. After 30 minutes, the addition of the same quantities of p-toluenesulfonic anhydride and tert-butylamine was repeated to complete the reaction. The reaction mixture was concentrated and partitioned between 100 ml of diethylether and 1 M aqueous sodium carbonate. The aqueous layer was extracted with 50 ml of diethylether again and combined organic extracts were washed with water, brine, dried over sodium sulfate and concentrated in vacuum. The residue was purified by flash chromatography eluting with 10% of ethyl acetate in hexane to give N-tert-butyl-5-iodo-4-(2-(thiophen-3-yl)ethoxy)pyridin-2-amine (0.473 g (52%). 1H NMR (400 MHz, CDCl3) δ 8.15 (s, 1H), 7.28 (dd, J=3.0, 4.8, 1H), 7.18 (s, 1H), 7.12 (d, J=4.9, 1H), 5.85 (s, 1H), 4.44 (s, 1H), 4.15 (t, J=6.5, 2H), 3.18 (t, J=6.5, 2H), 1.39 (s, 9H). MS: (ESI+) 403.2

Workup

  1. customthe reaction
  2. concentrationThe reaction mixture was concentrated
  3. custompartitioned between 100 ml of diethylether and 1 M aqueous sodium carbonate
  4. extractionThe aqueous layer was extracted with 50 ml of diethylether again
  5. washwere washed with water, brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuum
  8. customThe residue was purified by flash chromatography
  9. washeluting with 10% of ethyl acetate in hexane

Sources & evidence

ORD record
ord-3794d7bff55d4752b2db77f8855983f1
Source dataset
uspto-grants-2014_09
Patent number
US08846762B2

Linked notes

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