Hydrochloric Acid → 3-(2-{[6-chloro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl]amino}ethyl)phenol

HRID 2089001

반응식

HRID 2089001 반응식
Cl[C:2]1[CH:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[N:10](S(C3C=CC=CC=3)(=O)=O)[CH:9]=2)[CH:5]=[C:4]([Cl:26])[N:3]=1.[NH2:27][CH2:28][CH2:29][C:30]1[CH:31]=[C:32]([OH:36])[CH:33]=[CH:34][CH:35]=1.Cl.C(N(C(C)C)CC)(C)C>C(#N)C.[Cl-].[Na+].O>[Cl:26][C:4]1[N:3]=[C:2]([NH:27][CH2:28][CH2:29][C:30]2[CH:31]=[C:32]([OH:36])[CH:33]=[CH:34][CH:35]=2)[CH:7]=[C:6]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[NH:10][CH:9]=2)[CH:5]=1

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 11492m-TyramineHCID 81531DiisopropylethylamineHCID 866498693-(2,6-dichloropyridin-4-yl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine

생성물 1

HCID 509389383-(2-{[6-chloro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl]amino}ethyl)phenol

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 57417360Sodium chloride; water용매

반응 조건

온도
60 °C

실험 절차

A mixture of Example 7a (75.0 mg, 0.186 mmol), 3-(2-aminoethyl)phenol.HCl (0.250 g, 1.44 mmol), and diisopropylethylamine (0.52 mL, 2.97 mmol) in acetonitrile (0.6 mL) was heated in a Biotage microwave reactor at 160° C. for 30 minutes. The reaction mixture was treated with 20% brine and extracted with EtOAc (2×). The combined organic layers were washed with 20% brine, dried over MgSO4, filtered, and concentrated. The crude was dissolved in dioxane (1.3 mL) and treated with 20% NaOH (0.12 mL). The mixture was heated at 60° C. for 1 hour and concentrated. The residue was treated with water, sonicated, filtered, washed with water, and dried. The crude material was purified on a 4 g column using the ISCO Companion flash system eluting with CH2Cl2/MeOH (97:3 to 90:10) to give 5.5 mg of the title compound. 1H NMR (500 MHz, DMSO-d6) ppm 2.77 (t, J=7.32 Hz, 2H), 3.46 (t, J=6.87 Hz, 2H), 6.61 (d, J=7.93 Hz, 1H), 6.65-6.74 (m, 2H), 6.87 (s, 1H), 6.89-6.98 (m, 2H), 7.09 (t, J=7.78 Hz, 1H), 7.21 (dd, J=7.93, 4.88 Hz, 1H), 8.14 (d, J=2.75 Hz, 1H), 8.25-8.35 (m, 2H), 9.27 (s, 1H), 12.16 (s, 1H). MS (DCI+) m/z 365.0 (M+H)+.

후처리

  1. extractionextracted with EtOAc (2×)
  2. washThe combined organic layers were washed with 20% brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe crude was dissolved in dioxane (1.3 mL)
  7. additiontreated with 20% NaOH (0.12 mL)
  8. concentrationconcentrated
  9. additionThe residue was treated with water
  10. customsonicated
  11. filtrationfiltered
  12. washwashed with water
  13. customdried
  14. customThe crude material was purified on a 4 g column
  15. washeluting with CH2Cl2/MeOH (97:3 to 90:10)

출처 및 근거

ORD 기록
ord-9e99601d48f643039481602f15b88dcc
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08435980B2

연결된 노트

불러오는 중…