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Sodium Bicarbonate → (R)-4-(2-methyl-6-(3-methylpiperazin-1-yl)pyridin-3-yl)-6-(trifluoromethyl)-1H-indazole

HRID 58119
ノート
印刷プレビュー

反応式

HRID 58119 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]([N:9]2[CH2:14][CH2:13][NH:12][C@H:11]([CH3:15])[CH2:10]2)=[N:6][C:7]=1[CH3:8].[F:16][C:17]([F:31])([F:30])[C:18]1[CH:26]=[C:25]2[C:21]([CH:22]=[N:23][NH:24]2)=[C:20](B(O)O)[CH:19]=1.[C:32]([O-:35])(O)=[O:33].[Na+]>O1CCOCC1.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]>[C:32]([OH:35])([C:17]([F:31])([F:30])[F:16])=[O:33].[CH3:8][C:7]1[C:2]([C:20]2[CH:19]=[C:18]([C:17]([F:31])([F:30])[F:16])[CH:26]=[C:25]3[C:21]=2[CH:22]=[N:23][NH:24]3)=[CH:3][CH:4]=[C:5]([N:9]2[CH2:14][CH2:13][NH:12][C@H:11]([CH3:15])[CH2:10]2)[N:6]=1
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 516892Sodium BicarbonateHCID 89783507[6-(Trifluoromethyl)-1H-indazol-4-yl]boronic acidHCID 89794907(R)-1-(5-bromo-6-methylpyridin-2-yl)-3-methylpiperazine

生成物 2

HCID 6422Trifluoroacetic acidHCID 89794891(R)-4-(2-methyl-6-(3-methylpiperazin-1-yl)pyridin-3-yl)-6-(trifluoromethyl)-1H-indazole収率 29.2%

試薬・触媒・溶媒 2

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

反応条件

温度
145 °C

実験手順

In a 10 mL microwave vial were mixed (R)-1-(5-bromo-6-methylpyridin-2-yl)-3-methylpiperazine (120 mg, 0.444 mmol), (6-(trifluoromethyl)-1H-indazol-4-yl)boronic acid (133 mg, 0.577 mmol), PdCl2(dppf) (32.5 mg, 0.044 mmol), and aqueous NaHCO3 (0.950 mL, 1.777 mmol) in dioxane (10 mL) to give an orange suspension. The vial was sealed and heated in a microwave reactor to 145° C. for 45 minutes. The reaction mixture was then filtered and the product was purified by preparative HPLC, eluting with a gradient of 15-40% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA). The pure fractions were lyophilized to give a TFA salt of the title compound as a white solid (31.6 mg, 14.5%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.31 (d, J=6.57 Hz, 3H), 2.27 (s, 3H), 2.95 (dd, J=14.02, 10.48 Hz, 1H), 3.05-3.21 (m, 2H), 3.36 (d, J=7.33 Hz, 1H), 3.44 (d, J=11.62 Hz, 1H), 4.44 (d, J=13.14 Hz, 2H), 6.94 (d, J=8.59 Hz, 1H), 7.24 (d, J=1.52 Hz, 1H), 7.64 (d, J=8.59 Hz, 1H), 7.92-7.94 (m, 1H), 7.95 (d, J=1.01 Hz, 1H), 8.77 (d, J=8.59 Hz, 1H), 9.10 (d, J=8.34 Hz, 1H); ESI-MS m/z [M+H]+ calc'd for C19H20F3N5, 376.2. found 376.4.

後処理

  1. customto give an orange suspension
  2. customThe vial was sealed
  3. filtrationThe reaction mixture was then filtered
  4. customthe product was purified by preparative HPLC
  5. washeluting with a gradient of 15-40% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA)

出典と根拠

ORDレコード
ord-3b6739e8385a46cda3900b530fb52374
出典データセット
uspto-grants-2016_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09434743B2

反応ノート

読み込み中…

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