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Potassium Carbonate → 4-(4-{3-[1-(2,6-Dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-pyrazol-1-yl)cyclohexanone

HRID 2046950
ノート
印刷プレビュー

反応式

HRID 2046950 の反応式
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[CH:10]([C:12]1[C:20]2[C:15](=[N:16][CH:17]=[C:18](B3OC(C)(C)C(C)(C)O3)[CH:19]=2)[NH:14][CH:13]=1)[CH3:11].I[C:31]1[CH:32]=[N:33][N:34]([CH:36]2[CH2:41][CH2:40][C:39](=[O:42])[CH2:38][CH2:37]2)[CH:35]=1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[CH:10]([C:12]1[C:20]2[C:15](=[N:16][CH:17]=[C:18]([C:31]3[CH:32]=[N:33][N:34]([CH:36]4[CH2:37][CH2:38][C:39](=[O:42])[CH2:40][CH2:41]4)[CH:35]=3)[CH:19]=2)[NH:14][CH:13]=1)[CH3:11]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 584314473-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridineHCID 595411654-(4-iodo-1H-pyrazol-1-yl)cyclohexanone

生成物 1

HCID 673635814-(4-{3-[1-(2,6-Dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-pyrazol-1-yl)cyclohexanone

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒

反応条件

温度
90 °C

実験手順

A 20 ml sealable vial was charged with 3-[1-(2,6-Dichloro-3-fluorophenyl)ethyl]-5-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (80.0 mg, 0.156 mmol), 4-(4-Iodopyrazol-1-yl)cyclohexanone (52.5 mg, 0.172 mmol), Pd(PPh3)4 (12.0 mg, 0.0103 mmol), potassium carbonate (71.8 mg, 0.514 mmol), and 4:1 dioxane:water (5 mL). The cap was sealed and the vial was evacuated and backfilled with nitrogen (3×). After that, the vial was heated at 90° C. for 2 h. The reaction mixture was partitioned between EtOAc/H2O (15 ml/10 ml). The aqueous phase was extracted with EtOAc (10 ml). The combined organic extracts were washed with water (10 ml) and brine (10 ml), dried over MgSO4, filtered, and concentrated in vacuo to give a brown oil that was purified by prep. TLC eluting with 4% MeOH/DCM to give the title compound. 1H NMR (400 MHz, CDCl3): δ=1.88 (d, J=7.2 Hz, 3H), 2.31-2.68 (m, 8 H), 4.64 (tt, J=11.8, 4.0 Hz, 1 H), 5.28 (q, J=7.2 Hz, 1 H), 7.01 (dd, J=8.0 & 8.8 Hz, 1 H), 7.30 (s, 1 H), 7.32 (brs, 1 H), 7.48 (s, 1 H), 7.60 (d, J=0.8 Hz, 1 H), 7.66 (d, J=0.8 Hz, 1 H), 8.41 (brs, 1 H), 9.77 (brs, 1 H). MS (ES+): m/z=471.16/473.11 (100/68) [MH+]. HPLC: tR=3.39 min (polar—5 min, ZQ3).

後処理

  1. customThe cap was sealed
  2. customthe vial was evacuated
  3. customThe reaction mixture was partitioned between EtOAc/H2O (15 ml/10 ml)
  4. extractionThe aqueous phase was extracted with EtOAc (10 ml)
  5. washThe combined organic extracts were washed with water (10 ml) and brine (10 ml)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a brown oil that
  10. customwas purified by prep

出典と根拠

ORDレコード
ord-a685a2709d184cb5bfce511281b5ec17
出典データセット
uspto-grants-2013_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08592448B2

反応ノート

読み込み中…

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