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

HRID 2266144

반응식

HRID 2266144 반응식
[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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
100 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-4efa7c546986481caf40b9fb3518bf71
출처 데이터셋
uspto-grants-2010_12
특허 번호
US07858632B2

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