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

HRID 58107

반응식

HRID 58107 반응식
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

참가 물질

7

반응물 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

생성물 2

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

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 312751,4-Dioxane용매

반응 조건

온도
140 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-3485b525722f41fcacba80e09e92f30d
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434743B2

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