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 575137ノート

反応式

HRID 575137 の反応式
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

参加物

7

反応物 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

生成物 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

試薬・触媒・溶媒 3

HCID 70681Tetrabutylammonium Chloride触媒HCID 167845palladium(II) acetate触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
100 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-da4faa1363a0439cb8f7778a8f9e98e6
出典データセット
uspto-grants-2015_05
特許番号
US09034866B2

反応ノート

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