Triethylamine → 2-{4-[5-fluoro-4-(5-fluoro-2-methoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3,6-dihydropyridin-1(2H)-yl}-1-(4-hydroxypiperidin-1-yl)ethanone

HRID 1522036노트

반응식

HRID 1522036 반응식
[F:1][C:2]1[C:3]([C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=2[O:28][CH3:29])=[C:4]2[CH:10]=[C:9]([C:11]3[CH2:16][CH2:15][N:14]([CH2:17][C:18](O)=[O:19])[CH2:13][CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.C(N(CC)CC)C.Cl.[NH:71]1[CH2:76][CH2:75][CH:74]([OH:77])[CH2:73][CH2:72]1>CN(C)C=O.[Cl-].[Na+].O.O>[F:1][C:2]1[C:3]([C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=2[O:28][CH3:29])=[C:4]2[CH:10]=[C:9]([C:11]3[CH2:16][CH2:15][N:14]([CH2:17][C:18]([N:71]4[CH2:76][CH2:75][CH:74]([OH:77])[CH2:73][CH2:72]4)=[O:19])[CH2:13][CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1

참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 162124994-Hydroxypiperidinium chlorideHCID 90412424US9796708, Example 753

생성물 1

HCID 904139322-{4-[5-fluoro-4-(5-fluoro-2-methoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3,6-dihydropyridin-1(2H)-yl}-1-(4-hydroxypiperidin-1-yl)ethanone

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 57417360Sodium chloride; water용매

실험 절차

A mixture of Example 294A (0.085 g, 0.195 mmol), (benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (0.122 g, 0.234 mmol), triethylamine (0.109 mL, 0.780 mmol), and piperidin-4-ol.hydrochloride (0.032 g, 0.234 mmol) in N,N-dimethylformamide (2 mL) was stirred for 3 hours. The mixture was treated with water and brine and extracted with ethyl acetate (twice). The combined organic layers were washed with brine, dried over magnesium sulfate, filtered, concentrated, and purified on silica gel using the ISCO Companion eluting with dichloromethane/methanol/ammonium hydroxide (18:1:0.1 to 9:1:0.1) to give the title compound. 1H NMR (400 MHz, Methanol-d4) δ 1.33-1.60 (m, 2H), 1.79-1.94 (m, 2H), 2.56 (bs, 2H), 2.73-2.80 (m, 2H), 3.06-3.18 (m, 1H), 3.27-3.30 (m, 2H), 3.32-3.43 (m, 2H), 3.76 (s, 3H), 3.78-3.98 (m, 2H), 4.03-4.12 (m, 1H), 4.56 (d, J=1.1 Hz, 1H), 6.16 (s, 1H), 6.34-6.40 (m, 1H), 6.99-7.24 (m, 3H), 8.06 (d, J=2.9 Hz, 1H). MS (ESI+) m/z 483.1 (M+H)+.

후처리

  1. extractionextracted with ethyl acetate (twice)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified on silica gel using the ISCO Companion
  7. washeluting with dichloromethane/methanol/ammonium hydroxide (18:1:0.1 to 9:1:0.1)

출처 및 근거

ORD 기록
ord-4d30ae1dd8c3486382e563ed6c55bae9
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073922B2

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