Nitrogen → tert-Butyl 6-(4-(6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate

HRID 587113ノート

反応式

HRID 587113 の反応式
Br[C:2]1[CH:3]=[N:4][N:5]([CH:7]2[CH2:20][C:9]3([CH2:12][N:11]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:10]3)[CH2:8]2)[CH:6]=1.[Cl:21][C:22]1[C:27]([F:28])=[CH:26][CH:25]=[C:24]([Cl:29])[C:23]=1[CH:30]([O:32][C:33]1[C:34]([NH2:48])=[N:35][CH:36]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH:38]=1)[CH3:31].N#N.C([O-])([O-])=O.[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.COCCOC>[NH2:48][C:34]1[N:35]=[CH:36][C:37]([C:2]2[CH:3]=[N:4][N:5]([CH:7]3[CH2:20][C:9]4([CH2:12][N:11]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:10]4)[CH2:8]3)[CH:6]=2)=[CH:38][C:33]=1[O:32][CH:30]([C:23]1[C:24]([Cl:29])=[CH:25][CH:26]=[C:27]([F:28])[C:22]=1[Cl:21])[CH3:31]

参加物

7

反応物 4

HCID 947Nitrogen2 回HCID 10340Sodium CarbonateHCID 211113943-(1-(2,6-Dichloro-3-fluorophenyl)ethoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 71244309tert-butyl 6-(4-bromo-1H-pyrazol-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate

生成物 1

HCID 71240178tert-Butyl 6-(4-(6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate収率 45%

試薬・触媒・溶媒 2

HCID 178418476HCID 178418476、化合物触媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
90 °C

実験手順

tert-Butyl 6-(4-bromo-1H-pyrazol-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate (145 mg, 0.42 mmol) and (±)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (268 mg, 0.63 mmol) were added to a round bottom flask. It was vacuumed and refilled with N2 (3 times). DME (2.0 mL) and a solution of Na2CO3 (2.0 M, 1.0 mL) were sequentially added. It was vacuumed and refilled with N2 (3 times). Pd(PPh3)2Cl2 (14.7 mg, 0.021 mmol) was added. It was degassed again refilled with N2 (2 times). The mixture was stirred at 90° C. (heating bath) for 16 hrs. The reaction mixture was cooled to room temperature and H2O (30 mL) was added. The aqueous phase was extracted with EtOAc (30 mL) and DCM (3×30 mL). The combined organic phase was dried over anhydrous Na2SO4, concentrated by evaporation in vacuo to give black residue which was purified by CombiFlash (40 g silica gel column, Hexane/EtOAc) to afford (±)-tert-butyl 6-(4-(6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate (106 mg, 45%) as a off-white solid.

後処理

  1. customIt was degassed again
  2. additionrefilled with N2 (2 times)
  3. temperature(heating bath) for 16 hrs
  4. temperatureThe reaction mixture was cooled to room temperature
  5. additionH2O (30 mL) was added
  6. extractionThe aqueous phase was extracted with EtOAc (30 mL) and DCM (3×30 mL)
  7. dry with materialThe combined organic phase was dried over anhydrous Na2SO4
  8. concentrationconcentrated by evaporation in vacuo
  9. customto give black residue which
  10. customwas purified by CombiFlash (40 g silica gel column, Hexane/EtOAc)

出典と根拠

ORDレコード
ord-a37fc8f051724aec9244c9a4b3868890
出典データセット
uspto-grants-2016_01
特許番号
US09226923B2

反応ノート

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