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Potassium Carbonate → 3-(5-Chloro-8-fluoroisoquinolin-3-yl)-5-thiophen-3-ylpyridin-2-amine

HRID 1926323
ノート
印刷プレビュー

反応式

HRID 1926323 の反応式
Br[C:2]1[CH:3]=[C:4]([C:9]2[N:10]=[CH:11][C:12]3[C:17]([CH:18]=2)=[C:16]([Cl:19])[CH:15]=[CH:14][C:13]=3[F:20])[C:5]([NH2:8])=[N:6][CH:7]=1.[S:21]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22]1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:19][C:16]1[CH:15]=[CH:14][C:13]([F:20])=[C:12]2[C:17]=1[CH:18]=[C:9]([C:4]1[C:5]([NH2:8])=[N:6][CH:7]=[C:2]([C:23]3[CH:24]=[CH:25][S:21][CH:22]=3)[CH:3]=1)[N:10]=[CH:11]2
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 3

HCID 11430Potassium CarbonateHCID 581760Thiophene-3-boronic acidHCID 675207675-Bromo-3-(5-chloro-8-fluoroisoquinolin-3-yl)-pyridin-2-ylamine

生成物 1

HCID 675212113-(5-Chloro-8-fluoroisoquinolin-3-yl)-5-thiophen-3-ylpyridin-2-amine

試薬・触媒・溶媒 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
触媒
HCID 962Water溶媒
HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A mixture of 5-bromo-3-(5-chloro-8-fluoroisoquinolin-3-yl)-pyridin-2-ylamine (BB4) (25 mg, 0.070 mmol), 3-thienylboronic acid (20 mg, 0.10 mmol) and potassium carbonate (29 mg, 0.21 mmol) in 1,4-dioxane (1.0 mL) and H2O (0.4 mL) was degassed and refilled with argon (3×) prior to the addition of Pd(dppf)Cl2 (5 mg, 0.01 mmol). The reaction mixture was degassed and refilled with argon (2×) and left to stir at 100° C. in the microwave reactor for 30 min. Then, the mixture was passed through PL-Thiol MP SPE resin and concentrated in vacuo. The residual oil was partitioned between DCM and H2O. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. Purification via MDP afforded the title compound as a yellow solid. MS (ES+): m/z=356.03/358.05 (100/50) [MH+]. HPLC: tR=3.22 min (ZQ2, polar—5 min).

後処理

  1. customwas degassed
  2. additionrefilled with argon (3×)
  3. customThe reaction mixture was degassed
  4. additionrefilled with argon (2×)
  5. waitleft
  6. concentrationconcentrated in vacuo
  7. customThe residual oil was partitioned between DCM and H2O
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over anhydrous Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customPurification via MDP

出典と根拠

ORDレコード
ord-55a3989c98b049eeb61436478f1f8992
出典データセット
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08178668B2

反応ノート

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