Thiazole → 5-(5-Furan-2-yl-2-isopropyl-4-methoxy-phenoxy)-pyrimidine-2,4-diamine

HRID 81833Notes

Reaction equation

I[C:2]1[C:3]([O:20][CH3:21])=[CH:4][C:5]([CH:17]([CH3:19])[CH3:18])=[C:6]([CH:16]=1)[O:7][C:8]1[C:9]([NH2:15])=[N:10][C:11]([NH2:14])=[N:12][CH:13]=1.[C:22]([O-:25])(=O)[CH3:23].[K+].S1[CH:31]=[CH:30]N=C1>>[O:25]1[CH:22]=[CH:23][CH:31]=[C:30]1[C:2]1[C:3]([O:20][CH3:21])=[CH:4][C:5]([CH:17]([CH3:19])[CH3:18])=[C:6]([CH:16]=1)[O:7][C:8]1[C:9]([NH2:15])=[N:10][C:11]([NH2:14])=[N:12][CH:13]=1

Participants

Reactant 3

HCID 9256Thiazole

HCID 517044Potassium Acetate

HCID 159538025-(5-Iodo-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine

Product 1

HCID 573291135-(5-Furan-2-yl-2-isopropyl-4-methoxy-phenoxy)-pyrimidine-2,4-diamine

Conditions

Temperature: 155 °C

Procedure

5-(5-Iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidine-2,4-diamine (400 mg, 1.0 mmol), potassium acetate ((147 mg), Pd(Ph3)2Cl2 (40 mg in 2 mL dimethyl acetamide) and thiazole were added to a screw cap pressure vial and heated to 155° C. for 40 hours. The reaction mixture was cooled and partitioned between water and ethyl acetate. The organic phase was separated, dried (MgSO4), filtered, and evaporated under reduced pressure. The residue was purified by flash chromatography (3% to 5% MeOH in methylene chloride with 1% ammonium hydroxide) to yield 61 mg of 5-(5-Furan-2-yl-2-isopropyl-4-methoxy-phenoxy)-pyrimidine-2,4-diamine (M+H)=356. Mp=199.1-203.3° C.

Workup

customcap pressure vial
temperatureThe reaction mixture was cooled
custompartitioned between water and ethyl acetate
customThe organic phase was separated
dry with materialdried (MgSO4)
filtrationfiltered
customevaporated under reduced pressure
customThe residue was purified by flash chromatography (3% to 5% MeOH in methylene chloride with 1% ammonium hydroxide)

Sources & evidence

ORD record: ord-79702d108cf843f99a83c79ea459fcac
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846705B2

Reaction notes

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