Hydrochloric Acid → {1-piperidin-4-yl-3-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile trihydrochloride

HRID 1617371ノート

反応式

HRID 1617371 の反応式
[CH3:1][Si:2]([CH3:29])([CH3:28])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[C:11]2=[N:12][CH:13]=[CH:14][C:15]([C:16]3[CH:17]=[N:18][N:19]([C:21]4([CH2:25][C:26]#[N:27])[CH2:24][NH:23][CH2:22]4)[CH:20]=3)=[C:10]2[CH:9]=[CH:8]1.O=[C:31]1[CH2:36][CH2:35][N:34](C(OC(C)(C)C)=O)[CH2:33][CH2:32]1.C(N(CC)C(C)C)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[ClH:67].O1CCOCC1>C1COCC1>[ClH:67].[ClH:67].[ClH:67].[NH:34]1[CH2:35][CH2:36][CH:31]([N:23]2[CH2:22][C:21]([CH2:25][C:26]#[N:27])([N:19]3[CH:20]=[C:16]([C:15]4[CH:14]=[CH:13][N:12]=[C:11]5[N:7]([CH2:6][O:5][CH2:4][CH2:3][Si:2]([CH3:28])([CH3:1])[CH3:29])[CH:8]=[CH:9][C:10]=45)[CH:17]=[N:18]3)[CH2:24]2)[CH2:32][CH2:33]1

参加物

8

反応物 6

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 67420216{3-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile

生成物 1

HCID 67391063{1-piperidin-4-yl-3-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile trihydrochloride

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a mixture of {3-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile.2[HCl] (347 mg, 0.70 mmol), tert-butyl 4-oxo-1-piperidinecarboxylate (134 mg, 0.70 mmol) and N,N-diisopropylethylamine (0.467 mL, 2.68 mmol) in THF (10.0 mL) was added sodium triacetoxyborohydride (284 mg, 1.34 mmol). The mixture was stirred at room temperature for 2 hours and quenched with brine. The resulting solution was extracted with EtOAc (2 times). The combined extracts were washed with water, brine and dried over Na2SO4. After filtration and evaporation, the residue was purified by flash chromatography on silica gel eluting with 50-100% EtOAc/hexanes. The purified intermediate (MS: [M+H]+=592.3) was dissolved in THF (6 mL). To the solution was added a 4.0 M solution of HCl in 1,4-dioxane (6 mL, 24 mmol). The mixture was stirred at room temperature for 2 hours and concentrated to give 260 mg of {1-piperidin-4-yl-3-[4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile trihydrochloride as a yellowish solid. LC/MS found: 492.0 (M+H)+. 1H NMR (400 MHz, DMSO-d6), δ 9.45 (s, 1H), 8.96 (s, 1H), 8.73 (s, 1H), 8.35 (d, 1H), 8.46 (s, 1H), 8.33 (d, 1H), 7.81 (d, 1H), 7.50 (d, 1H), 7.10 (m, 1H), 5.69 (s, 2H), 4.93 (d, 2H), 4.54 (d, 2H), 3.75-3.60 (m, 1H), 3.55 (s, 2H), 3.55 (s, 2H), 3.52 (t, 2H), 3.49-3.37 (m, 2H), 2.81 (m, 2H), 2.12 (d, 2H), 1.80 (m, 2H), 0.82 (t, 2H), −0.11 (s, 9H).

後処理

  1. customquenched with brine
  2. extractionThe resulting solution was extracted with EtOAc (2 times)
  3. washThe combined extracts were washed with water, brine
  4. dry with materialdried over Na2SO4
  5. filtrationAfter filtration and evaporation
  6. customthe residue was purified by flash chromatography on silica gel eluting with 50-100% EtOAc/hexanes
  7. dissolutionThe purified intermediate (MS: [M+H]+=592.3) was dissolved in THF (6 mL)
  8. stirringThe mixture was stirred at room temperature for 2 hours
  9. concentrationconcentrated

出典と根拠

ORDレコード
ord-b0182bbda4134b4eb14ddfb10a17130d
出典データセット
uspto-grants-2014_07
特許番号
US08765734B2

反応ノート

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