Sodium hydride → 5-[1-(3-Methoxy-propyl)-1H-pyrazol-4-yl]-2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine

HRID 1505700노트

반응식

HRID 1505700 반응식
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[C:9]([C:13]3[N:18]=[CH:17][C:16]([C:19]4[CH:20]=[N:21][NH:22][CH:23]=4)=[CH:15][N:14]=3)[CH:10]=[CH:11][CH:12]=2)[CH:4]=[N:3]1.[H-].[Na+].Cl[CH2:27][CH2:28][CH2:29][O:30][CH3:31]>CN(C=O)C>[CH3:31][O:30][CH2:29][CH2:28][CH2:27][N:21]1[CH:20]=[C:19]([C:16]2[CH:17]=[N:18][C:13]([C:9]3[CH:10]=[CH:11][CH:12]=[C:7]([C:5]4[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=4)[CH:8]=3)=[N:14][CH:15]=2)[CH:23]=[N:22]1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 1189271-Chloro-3-methoxypropaneHCID 729446552-[3-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-(1H-pyrazol-4-yl)pyrimidine

생성물 1

HCID 729442235-[1-(3-Methoxy-propyl)-1H-pyrazol-4-yl]-2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine

시약·촉매·용매 1

HCID 6228Dimethylformamide용매3회

반응 조건

온도
0 °C

실험 절차

A solution of 2-[3-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-(1H-pyrazol-4-yl)pyrimidine (example 3, 130 mg; 0.43 mmol; 1.0 eq.) in dry DMF (1 mL) was added over a suspension of NaH (60% in oil, 21 mg; 0.86 mmol; 2.0 eq.) in dry DMF (1 mL) maintained at 0° C. under nitrogen atmosphere. The resulting mixture was stirred for one hour at 0° C. then heated at 100° C. O/N after the addition of a solution of 1-chloro-3-methoxypropane (47 mg; 0.43 mmol; 1.0 eq.) in DMF (2 mL). Reaction mixture was then cooled down to RT, quenched with water and extracted with EtOAc (three times). Combined organic phases were washed with water, brine, dried over magnesium sulfate, filtered and concentrated. The resulting solid was dried O/N at 60° C. under reduced pressure to give the title compound a beige powder (165 mg; 75%). 1H NMR (300 MHz, DMSO-d6) δ 9.16 (s, 2H), 8.58-8.49 (m, 1H), 8.46 (s, 1H), 8.30-8.17 (m, 2H), 8.17-8.11 (m, 1H), 7.96-7.89 (m, 1H), 7.75-7.68 (m, 1H), 7.51 (t, J=7.8 Hz, 1H), 4.22 (t, J=7.0 Hz, 2H), 3.90 (s, 3H), 3.39-3.30 (m, 2H), 3.25 (s, 3H), 2.15-1.97 (m, 2H). HPLC (Condition A): Rt 3.34 min (purity 97.1%). MS (ESI+): 375.5.

후처리

  1. temperaturethen heated at 100° C
  2. customReaction mixture
  3. temperaturewas then cooled down to RT
  4. customquenched with water
  5. extractionextracted with EtOAc (three times)
  6. washCombined organic phases were washed with water, brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting solid was dried O/N at 60° C. under reduced pressure

출처 및 근거

ORD 기록
ord-55f9c2401fef4908a4809f7fa2a96d7e
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09216991B2

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