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 1522036ノート

反応式

HRID 1522036 の反応式
[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

参加物

8

反応物 4

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

生成物 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

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 57417360Sodium chloride; water溶媒

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-4d30ae1dd8c3486382e563ed6c55bae9
出典データセット
uspto-grants-2015_07
特許番号
US09073922B2

反応ノート

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