Sodium Bicarbonate → HCID 89794891, 화합물

HRID 58119

반응식

HRID 58119 반응식
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

참가 물질

7

반응물 3

HCID 516892Sodium BicarbonateHCID 89783507HCID 89783507, 화합물HCID 89794907(R)-1-(5-bromo-6-methylpyridin-2-yl)-3-methylpiperazine

생성물 2

HCID 6422Trifluoroacetic acidHCID 89794891HCID 89794891, 화합물수율 29.2%

시약·촉매·용매 2

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

반응 조건

온도
145 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-3b6739e8385a46cda3900b530fb52374
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434743B2

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