Benzenamine hydrochloride (1:1) → 5-(2-Isopropyl-4-methoxy-5-thiazol-4-yl-phenoxy)-pyrimidine-2,4-diamine

HRID 2266144Notes

Reaction equation

HRID 2266144 reaction equation
[CH:1]([C:4]1[CH:13]=[C:12]([O:14][CH3:15])[C:11]([C:16]2[N:17]=[CH:18][S:19][CH:20]=2)=[CH:10][C:5]=1[O:6][CH2:7][C:8]#[N:9])([CH3:3])[CH3:2].CC(O[CH:26]([N:30]([CH3:32])C)[N:27](C)C)(C)C.Cl.[NH2:34]C1C=CC=CC=1.C(=O)(O)O.NC(N)=N>O.CN1C(=O)CCC1>[CH:1]([C:4]1[CH:13]=[C:12]([O:14][CH3:15])[C:11]([C:16]2[N:17]=[CH:18][S:19][CH:20]=2)=[CH:10][C:5]=1[O:6][C:7]1[C:26]([NH2:27])=[N:30][C:32]([NH2:34])=[N:9][CH:8]=1)([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 8870Benzenamine hydrochloride (1:1)HCID 79885tert-Butoxy bis(dimethylamino)methaneHCID 286947Carbonic acid-guanidine (1:1)HCID 59598608(2-Isopropyl-4-methoxy-5-thiazol-4-yl-phenoxy)-acetonitrile

Product 1

HCID 595986345-(2-Isopropyl-4-methoxy-5-thiazol-4-yl-phenoxy)-pyrimidine-2,4-diamineYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (2-Isopropyl-4-methoxy-5-thiazol-4-yl-phenoxy)-acetonitrile (0.27 g, 0.94 mmol) and Brederick's reagent (0.35 g, 2.01 mmol) was heated at 100° C. for 2 hrs. Excess Brederick's reagent was removed under reduced pressure. The residue was dissolved in anhydrous EtOH (10 ml) and aniline HCl (0.38 g, 2.93 mmol) was added. The reaction mixture was heated at 80° C. for 18 hrs and partitioned between EtOAc and water. The combined organic extracts were dried over Na2SO4, filtered and concentrated. Guanidine carbonate (0.27 g,1.49 mmol) and NMP (10 ml) were added and heated to 120° C. for 10 hrs. The reaction mixture was poured into water and extracted into EtOAc. The combined organic extracts were dried over Na2SO4, filtered and concentrated. Flash chromatography on silica (3% MeOH in methylene chloride with 0.1% NH4OH) gave 5-(2-Isopropyl-4-methoxy-5-thiazol-4-yl-phenoxy)-pyrimidine-2,4-diamine (0.15 g, 68%) as a solid. (M+H)=358.

Workup

  1. customExcess Brederick's reagent was removed under reduced pressure
  2. dissolutionThe residue was dissolved in anhydrous EtOH (10 ml)
  3. temperatureThe reaction mixture was heated at 80° C. for 18 hrs
  4. custompartitioned between EtOAc and water
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. temperatureheated to 120° C. for 10 hrs
  9. extractionextracted into EtOAc
  10. dry with materialThe combined organic extracts were dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-4efa7c546986481caf40b9fb3518bf71
Source dataset
uspto-grants-2010_12
Patent number
US07858632B2

Reaction notes

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