Guanidine Hydrochloride → 5-(4-Ethyl-7-methyl-benzo[b]thiophen-5-yloxy)-pyrimidine-2,4-diamine

HRID 81845

Reaction equation

HRID 81845 reaction equation
[CH2:1]([C:3]1[C:11]2[CH:10]=[CH:9][S:8][C:7]=2[C:6]([CH3:12])=[CH:5][C:4]=1[O:13][C:14](=[CH:17]NC1C=CC=CC=1)[C:15]#[N:16])[CH3:2].Cl.[NH2:26][C:27]([NH2:29])=[NH:28].C[O-].[Na+]>C(O)C.O>[CH2:1]([C:3]1[C:11]2[CH:10]=[CH:9][S:8][C:7]=2[C:6]([CH3:12])=[CH:5][C:4]=1[O:13][C:14]1[C:15]([NH2:16])=[N:28][C:27]([NH2:29])=[N:26][CH:17]=1)[CH3:2]

Participants

6

Reactant 3

HCID 5742Guanidine Hydrochloride2×HCID 10942334Sodium Methoxide2×HCID 670534132-(4-Ethyl-7-methyl-benzo[b]thiophen-5-yloxy)-3-phenylamino-acrylonitrile

Product 1

HCID 161192635-(4-Ethyl-7-methyl-benzo[b]thiophen-5-yloxy)-pyrimidine-2,4-diamineYield 80.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent3×HCID 962WaterSolvent

Procedure

2-(4-Ethyl-7-methyl-benzo[b]thiophen-5-yloxy)-3-phenylamino-acrylonitrile (360 mg, 1 mmol), guanidine HCl (411 mg, 4 mmol) and sodium methoxide (880 ul, 4 mmol, 4.9 M solution in methanol) in 5 mL absolute ethanol were heated to reflux in 5 ml absolute ethanol for 2 hours. Premixed guanidine HCl (411 mg, 4 mmol) and sodium methoxide (880 ul, 4 mmol, 4.9 M solution in methanol) in 1 ml EtOH was added via pipette, and the reaction mixture was heated to reflux for 2 hours. The reaction mixture was cooled, diluted with water, extracted twice with EtOAc, washed with brine, and dried over magnesium sulfate. Solvent was removed in vacuo to give 241 mg of 5-(4-Ethyl-7-methyl-benzo[b]thiophen-5-yloxy)-pyrimidine-2,4-diamine as a white solid (74%). Mass Spec M+H=301, M.P.=181° C. Recrystallization of 175 mg of this product from MeOH and HCl/diethyl ether afforded 98 mg of the corresponding HCl salt 49%., Mass Spec M+H=301, M.P. >300 C.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 2 hours
  3. temperatureThe reaction mixture was cooled
  4. extractionextracted twice with EtOAc
  5. washwashed with brine
  6. dry with materialdried over magnesium sulfate
  7. customSolvent was removed in vacuo

Sources & evidence

ORD record
ord-4db89416827c4cdca96e7173e87d663f
Source dataset
uspto-grants-2014_09
Patent number
US08846705B2

Linked notes

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