Nitrogen → HCID 67520656、化合物

HRID 1926407ノート

反応式

HRID 1926407 の反応式
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[N:21][C:22]([NH2:34])=[C:23](B4OC(C)(C)C(C)(C)O4)[CH:24]=3)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl[C:36]1[S:37][C:38]2[C:44]([F:45])=[CH:43][CH:42]=[C:41]([C:46]([F:49])([F:48])[F:47])[C:39]=2[N:40]=1.C(=O)([O-])[O-].[K+].[K+].N#N>O1CCOCC1.O>[F:45][C:44]1[C:38]2[S:37][C:36]([C:23]3[C:22]([NH2:34])=[N:21][CH:20]=[C:19]([C:17]4[CH:16]=[N:15][N:14]([CH:11]5[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]5)[CH:18]=4)[CH:24]=3)=[N:40][C:39]=2[C:41]([C:46]([F:49])([F:47])[F:48])=[CH:42][CH:43]=1

参加物

7

反応物 4

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 534879604-[4-[6-Amino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridin-3-yl]pyrazol-1-yl]piperidine-1-carboxylic acid tert-butyl esterHCID 675207732-Chloro-7-fluoro-4-trifluoromethyl-1,3-benzothiazole

生成物 1

HCID 67520656HCID 67520656、化合物

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

To a solution of 4-{4-[6-amino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (BB8) (60 mg, 0.127 mmol, 1 eq), 2-chloro-7-fluoro-4-trifluoromethyl-1,3-benzothiazole (42 mg, 0.153 mmol, 1.2 eq), and potassium carbonate (43 mg, 0.317 mmol, 2.5 eq) in 20% aq. dioxane (15 mL) was bubbledN2 gas for 15 min. Catalyst PdCl2dppf (5 mol %) was added to the stirred solution and N2 gas bubbling continued for another 10 min. The reaction mixture was then heated at 80° C. for 2 h. Cooling of the reaction mixture and evaporation of dioxane under reduced pressure yielded a brown residue. It was diluted with water (50 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with water (20 mL) and brine (20 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to yield a yellowish-green solid. It was purified by column chromatography (50% ethyl acetate in hexane) to afford the BOC-protected title compound as yellowish-green solid; MS(ES+): m/z=563 [MH+]. To a solution of this Boc derivative (40 mg, 0.07 mmol) at 0-5° C. in dry DCM (10 ml) was added 4M HCl in dioxane (0.2 ml) dropwise and stirred the reaction mixture overnight at rt. Removed solvent under reduced pressure to afford the title compound as yellow solid. 1H NMR (400 MHz, DMSO-d6): δ=9.06-8.96 (brm, 1H), 8.85-8.73 (brm, 1H), 8.61 (d, J=2.0 Hz, 1H), 8.42 (s, 1H), 8.41 (d, J=2.0 Hz, 1H), 8.17 (very brs, 1H), 8.09 (s, 1H), 8.03 (dd, J=5.2, 8.4 Hz, 1H), 7.59 (t, J=8.4 Hz, 1H), 4.56-4.46 (mc, 1H), 3.41 (brd, J=12.4 Hz, 2H), 3.12 (brq, J=11.4 Hz, 2H), 2.31-2.11 (m, 4H). MS(ES+): m/z=463.05 (100) [MH+], 380.02 (80) [MH+-piperidine]. HPLC: tR=2.29 min (polar—5 min, ZQ2).

後処理

  1. customfor 15 min
  2. custombubbling
  3. temperatureCooling of the reaction mixture and evaporation of dioxane under reduced pressure
  4. customyielded a brown residue
  5. extractionextracted with ethyl acetate (3×20 mL)
  6. washThe combined organic layers were washed with water (20 mL) and brine (20 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto yield a yellowish-green solid
  11. customIt was purified by column chromatography (50% ethyl acetate in hexane)

出典と根拠

ORDレコード
ord-19dd0f064b1f4ffa8a54a956b2dfefdb
出典データセット
uspto-grants-2012_05
特許番号
US08178668B2

反応ノート

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