Sodium Bicarbonate → 4-(3,5-dimethyl-1-((3-methyloxetan-3-yl)methyl)-1H-pyrazol-4-yl)-6-(trifluoromethyl)-1H-indazole

HRID 58107

反応式

HRID 58107 の反応式
CC1(C)C(C)(C)OB([C:9]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[C:14]3[C:10]=2[CH:11]=[N:12][NH:13]3)O1.Br[C:24]1[C:25]([CH3:36])=[N:26][N:27]([CH2:30][C:31]2([CH3:35])[CH2:34][O:33][CH2:32]2)[C:28]=1[CH3:29].[C:37](=[O:40])(O)[O-:38].[Na+]>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].O1CCOCC1>[C:37]([OH:38])([C:18]([F:21])([F:20])[F:19])=[O:40].[CH3:36][C:25]1[C:24]([C:9]2[CH:17]=[C:16]([C:18]([F:19])([F:20])[F:21])[CH:15]=[C:14]3[C:10]=2[CH:11]=[N:12][NH:13]3)=[C:28]([CH3:29])[N:27]([CH2:30][C:31]2([CH3:35])[CH2:34][O:33][CH2:32]2)[N:26]=1

参加物

7

反応物 3

HCID 516892Sodium BicarbonateHCID 897828064-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazoleHCID 897828264-Bromo-3,5-dimethyl-1-[(3-methyl-3-oxetanyl)methyl]-1H-pyrazole

生成物 2

HCID 6422Trifluoroacetic acidHCID 897834294-(3,5-dimethyl-1-((3-methyloxetan-3-yl)methyl)-1H-pyrazol-4-yl)-6-(trifluoromethyl)-1H-indazole収率 28.5%

試薬・触媒・溶媒 2

HCID 178418228Bis(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
140 °C

実験手順

To a 5 mL vial equipped with a magnetic stir bar were added 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole (41.6 mg, 0.133 mmol), 4-bromo-3,5-dimethyl-1-((3-methyloxetan-3-yl)methyl)-1H-pyrazole (51.8 mg, 0.2 mmol), sodium bicarbonate (0.285 mL, 0.533 mmol), PdCl2(dppf) (9.76 mg, 0.013 mmol), and dioxane (3 mL). The contents of the vial were stirred to give an orange suspension. The vial was sealed and then heated in a microwave reactor at 140° C. for 90 minutes. The reaction mixture was subsequently filtered and the product was purified by preparative HPLC, eluting with a gradient of 25-50% 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 clear glass (6.9 mg, 11%). 1H NMR (400 MHz, CD3OD) δ ppm 1.46 (s, 3H), 2.37 (s, 6H), 3.71 (s, 2H), 4.31 (d, J=11.37 Hz, 2H), 4.58 (d, J=11.37 Hz, 2H), 7.39 (d, J=1.01 Hz, 1H), 8.04-8.06 (m, 1H), 8.07 (d, J=0.76 Hz, 1H); ESI-MS m/z [M+H]+ calc'd for C18H19F3N4O, 365.2. found 365.3.

後処理

  1. customTo a 5 mL vial equipped with a magnetic stir bar
  2. customto give an orange suspension
  3. customThe vial was sealed
  4. filtrationThe reaction mixture was subsequently filtered
  5. customthe product was purified by preparative HPLC
  6. washeluting with a gradient of 25-50% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA)

出典と根拠

ORDレコード
ord-3485b525722f41fcacba80e09e92f30d
出典データセット
uspto-grants-2016_09
特許番号
US09434743B2

関連ノート

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