Potassium Carbonate → HCID 90341022, compound

HRID 595696Notes

Reaction equation

HRID 595696 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:31]([C:32]([NH:34][CH3:35])=[O:33])=[C:11]3[CH:12]=[C:13](B4OC(C)(C)C(C)(C)O4)[C:14]([N:16]([CH3:21])[S:17]([CH3:20])(=[O:19])=[O:18])=[CH:15][N:10]3[N:9]=2)=[CH:4][CH:3]=1.Cl[C:37]1[CH:46]=[CH:45][C:44]2[CH2:43][CH2:42][N:41]3[C:47]4[CH:48]=[CH:49][CH:50]=[C:51]([F:54])[C:52]=4[CH:53]=[C:40]3[C:39]=2[N:38]=1.C([O-])([O-])=O.[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:54][C:51]1[C:52]2[CH:53]=[C:40]3[C:39]4[N:38]=[C:37]([C:13]5[C:14]([N:16]([CH3:21])[S:17]([CH3:20])(=[O:18])=[O:19])=[CH:15][N:10]6[N:9]=[C:8]([C:5]7[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=7)[C:31]([C:32]([NH:34][CH3:35])=[O:33])=[C:11]6[CH:12]=5)[CH:46]=[CH:45][C:44]=4[CH2:43][CH2:42][N:41]3[C:47]=2[CH:48]=[CH:49][CH:50]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 90333448HCID 90333448, compoundHCID 903336312-Chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine

Product 1

HCID 90341022HCID 90341022, compoundYield 45.3%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide (110 mg, 0.22 mmol), 2-chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine (50 mg, 0.18 mmol) and K2CO3 (50 mg, 0.366 mmol) in 1,4-dioxane (2 mL) were added X-Phos (10 mg) and Pd2(dba)3 (10 mg) under N2. The reaction mixture was stirred at 100° C. for 5 hours and concentrated in vacuo to remove 1,4-dioxane. The reaction mixture was extracted with EtOAc, washed with brine, dried over Na2SO4, filtered and evaporated concentrated in vacuo. The residue was purified by prep-HPLC to give the desired product (50 mg, yield: 44%). 1H-NMR (CDCl3, 400 MHz) δ 8.67 (s, 1H), 8.51 (s, 1H), 7.70˜7.73 (m, 3H), 7.52 (d, J=8.0 Hz, 1H), 7.27 (s, 1H), 7.23 (s, 1H), 7.14˜7.20 (m, 3H), 6.80 (t, J=8.0 Hz, 1H), 5.56 (br s, 1H), 4.36 (t, J=6.4 Hz, 2H), 3.51 (s, 3H), 3.34 (t, J=6.4 Hz, 2H), 2.85 (d, J=4.8 Hz, 3H), 2.63 (s, 3H). MS (M+H)+: 613.

Workup

  1. concentrationconcentrated in vacuo
  2. customto remove 1,4-dioxane
  3. extractionThe reaction mixture was extracted with EtOAc
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-9e8f397a5ded4d93b077d22b5f9aa300
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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