Sodium Acetate → (+/-) 10-Fluoro-9-(4-fluoro-3-hydroxy-3-methylbut-1-yn-1-yl)-2,5-diazatetracyclo[11.1.1.0[2,6].0[7,12]]pentadeca-3,5,7(12),8,10-pentaene-4-carboxamide

HRID 575137노트

반응식

HRID 575137 반응식
Br[C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][C:15]=1[F:16])[CH:12]1[CH2:17][CH:10]([CH2:11]1)[N:9]1[C:5]2=[N:6][C:7]([C:18]([NH2:20])=[O:19])=[CH:8]1.C([O-])(=O)C.[Na+].[F:26][CH2:27][C:28]([CH3:39])([OH:38])[C:29]#[C:30][Si](CC)(CC)CC>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C>[F:16][C:15]1[C:2]([C:30]#[C:29][C:28]([OH:38])([CH3:39])[CH2:27][F:26])=[CH:3][C:4]2[C:5]3[N:9]([CH:10]4[CH2:17][CH:12]([C:13]=2[CH:14]=1)[CH2:11]4)[CH:8]=[C:7]([C:18]([NH2:20])=[O:19])[N:6]=3

참가 물질

7

반응물 3

HCID 517045Sodium AcetateHCID 8669308010-bromo-9-fluoro-6,7-dihydro-5H-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamideHCID 86693093Fluoro-2-methyl-4-triethylsilyl-but-3-yn-2-ol

생성물 1

HCID 71715502(+/-) 10-Fluoro-9-(4-fluoro-3-hydroxy-3-methylbut-1-yn-1-yl)-2,5-diazatetracyclo[11.1.1.0[2,6].0[7,12]]pentadeca-3,5,7(12),8,10-pentaene-4-carboxamide

시약·촉매·용매 3

HCID 70681Tetrabutylammonium Chloride촉매HCID 167845palladium(II) acetate촉매HCID 6228Dimethylformamide용매

반응 조건

온도
100 °C

실험 절차

To a vial containing 9-bromo-10-fluoro-2,5-diazatetracyclo[11.1.1.0[2,6].0[7,12]]pentadeca-3,5,7,9,11-pentaene-4-carboxamide (0.1 g), palladium acetate (0.05 eq), sodium acetate (4 eq) and tetrabutylammonium chloride (1 eq) was added DMF (15 mL/mmol) and 1-fluoro-2-methyl-4-triethylsilyl-but-3-yn-2-ol (2 eq) dropwise. The reaction was sealed and heated to 100° C. for 15 minutes in a biotage microwave. The reaction mixture was extracted with DCM and saturated ammonium chloride. The organic layer was dried with magnesium sulfate, filtered, concentrated to dryness and purified by reverse phase hplc to afford (±) 10-fluoro-9-(4-fluoro-3-hydroxy-3-methylbut-1-yn-1-yl)-2,5-diazatetracyclo[11.1.1.0[2,6].0[7,12]]pentadeca-3,5,7(12),8,10-pentaene-4-carboxamide. MS (Q1) 358 (M)+. 1H NMR (400 MHz, DMSO) δ 8.67 (d, J=7.6 Hz, 1H), 7.82 (s, 1H), 7.53 (s, 1H), 7.30 (d, J=10.2 Hz, 1H), 7.10 (s, 1H), 6.01 (s, 1H), 4.91 (q, J=10.6, 6.2 Hz, 1H), 4.48-4.37 (m, 1H), 4.37-4.27 (m, 1H), 3.78-3.64 (m, 1H), 3.15-2.99 (m, 2H), 1.68 (d, J=12.2 Hz, 2H), 1.50 (s, 3H).

후처리

  1. customThe reaction was sealed
  2. extractionThe reaction mixture was extracted with DCM and saturated ammonium chloride
  3. dry with materialThe organic layer was dried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. custompurified by reverse phase

출처 및 근거

ORD 기록
ord-da4faa1363a0439cb8f7778a8f9e98e6
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09034866B2

반응 노트

불러오는 중…