Methanol → HCID 57678441, compound

HRID 491499Notes

Reaction equation

HRID 491499 reaction equation
[I:1][C:2]1[CH:11]=[CH:10][C:9]([I:12])=[CH:8][C:3]=1[O:4][CH2:5][C:6]#[N:7].C(O[CH:18]([N:22]([CH3:24])C)[N:19](C)C)(C)(C)C.Cl.NC1C=CC=CC=1.Cl.[NH2:34]C(N)=N.[O:38]([CH3:40])[Na].CO>C(O)C.O>[I:1][C:2]1[CH:11]=[C:10]([O:38][CH3:40])[C:9]([I:12])=[CH:8][C:3]=1[O:4][C:5]1[C:18]([NH2:19])=[N:22][C:24]([NH2:34])=[N:7][CH:6]=1

Participants

9

Reactant 6

HCID 887MethanolHCID 5742Guanidine HydrochlorideHCID 8870Benzenamine hydrochloride (1:1)HCID 79885tert-Butoxy bis(dimethylamino)methaneHCID 57678408HCID 57678408, compoundHCID 178418582HCID 178418582, compound

Product 1

HCID 57678441HCID 57678441, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (2,5-diiodo-phenoxy)-acetonitrile (1.15 g, 2.99 mmol) and tert-butoxybis(dimethylamino)methane (Bredrick's reagent, 2.08 g, 11.95 mmol) was heated to 100° C. under nitrogen for 18 hours. The reaction mixture was cooled and concentrated under reduced pressure. To the residue was added aniline hydrochloride (1.162 g, 8.97 mmol) and EtOH (20 mL). The resulting mixture was heated to reflux for 20 hours under nitrogen atmosphere. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. A mixture of guanidine hydrochloride (1.43 g, 14.95 mmol) and 25% NaOCH3 in methanol (3.3 mL, 14.95 mmol) in 7 mL ethanol was added to the residue, and the resulting mixture was heated to reflux under nitrogen for 18 hours. The reaction mixture was cooled, poured into water and extracted with EtOAc. The combined organic layers were washed with water and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was chomatographed on silica gel (30% CH2Cl2 in hexanes with 0.1% NH4OH) to give 0.64 g of 5-(2,5-diiodo-4-methoxy-phenoxy)-pyrimidine-2,4-diamine, MP=136-138° C. MS (M+H)=455.

Workup

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated under reduced pressure
  3. temperatureThe resulting mixture was heated
  4. temperatureto reflux for 20 hours under nitrogen atmosphere
  5. temperatureThe reaction mixture was cooled to room temperature
  6. concentrationconcentrated under reduced pressure
  7. additionwas added to the residue
  8. temperaturethe resulting mixture was heated
  9. temperatureto reflux under nitrogen for 18 hours
  10. temperatureThe reaction mixture was cooled
  11. extractionextracted with EtOAc
  12. washThe combined organic layers were washed with water and brine
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-8b090377e91741779ef6063cdf760855
Source dataset
uspto-grants-2009_05
Patent number
US07531547B2

Reaction notes

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