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 575137Notes

Reaction equation

HRID 575137 reaction equation
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

Participants

7

Reactant 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

Product 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

Reagents, catalysts & solvents 3

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-da4faa1363a0439cb8f7778a8f9e98e6
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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