Cesium carbonate → HCID 71557132, compound

HRID 1024052Notes

Reaction equation

HRID 1024052 reaction equation
C([O:4][CH2:5][C:6]1[C:11]([N:12]2[CH2:17][CH2:16][C:15]3[C:18]4[CH2:24][CH2:23][CH2:22][CH2:21][C:19]=4[S:20][C:14]=3[C:13]2=[O:25])=[CH:10][C:9]([F:26])=[CH:8][C:7]=1B1OC(C)(C)C(C)(C)O1)(=O)C.Cl[C:37]1[CH:38]=[C:39]([NH:46][C:47]2[CH:52]=[CH:51][C:50]([N:53]3[CH2:58][CH2:57][N:56]([CH:59]4[CH2:62][O:61][CH2:60]4)[CH2:55][CH2:54]3)=[CH:49][N:48]=2)[C:40]2[N:41]([CH:43]=[CH:44][N:45]=2)[N:42]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C([O-])([O-])=O.[Cs+].[Cs+]>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].O1CCOCC1>[F:26][C:9]1[CH:8]=[C:7]([C:37]2[CH:38]=[C:39]([NH:46][C:47]3[CH:52]=[CH:51][C:50]([N:53]4[CH2:58][CH2:57][N:56]([CH:59]5[CH2:62][O:61][CH2:60]5)[CH2:55][CH2:54]4)=[CH:49][N:48]=3)[C:40]3[N:41]([CH:43]=[CH:44][N:45]=3)[N:42]=2)[C:6]([CH2:5][OH:4])=[C:11]([N:12]2[C:13](=[O:25])[C:14]3[S:20][C:19]4[CH2:21][CH2:22][CH2:23][CH2:24][C:18]=4[C:15]=3[CH2:16][CH2:17]2)[CH:10]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 75806TricyclohexylphosphineHCID 670162052-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-4-fluoro-6-(1-oxo-3,4,5,6,7,8-hexahydrobenzothieno[2,3-c]pyridin-2(1H)-yl)benzyl AcetateHCID 866841246-Chloro-N-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine

Product 1

HCID 71557132HCID 71557132, compoundYield 22%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

A sealed tube equipped with a magnetic stirrer was charged with (4-fluoro-2-{6-oxo-8-thia-5-azatricyclo[7.4.0.02,7]trideca-1(9),2(7)-dien-5-yl}-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methyl acetate 103g (200 mg, 0.44 mmol), 6-chloro-N-(5-(4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine 108a (155 mg, 0.44 mmol), tricyclohexylphosphine (112 mg, 0.4 mmol), Pd2(dba)3 (28 mg, 0.024 mmol), Cs2CO3 (261 mg, 0.8 mmol), and dioxane (25 mL). After three cycles of vacuum/argon flash, the reaction mixture was heated at 110° C. for 16 h. The mixture was then evaporated in vacuo and the residue was extracted with Ethyl acetate (10 mL×2). The combined Ethyl acetate extract was concentrated under reduced pressure and the residue was purified with reverse-phase prep-HPLC to afford 111 (59 mg, 22%). MS: [M+H]+ 681. 1H NMR (500 MHz, DMSO) δ 9.94 (s, 1H), 8.23 (s, 1H), 8.16 (s, 1H), 8.02 (s, 1H), 7.67 (s, 1H), 7.44-7.46 (m, 3H), 7.34-7.36 (m, 1H), 4.64-4.66 (m, 1H), 4.54-4.57 (m, 2H), 4.42-4.48 (m, 3H), 4.35-4.38 (m, 1H), 3.96-4.10 (m, 1H), 3.79-3.89 (m, 1H), 3.42-3.45 (m, 1H), 3.14-3.16 (m, 4H), 2.54-2.96 (m, 4H), 2.47-2.50 (m, 2H), 2.37-2.41 (m, 4H), 1.79 (t, J=4.0, 4H)

Workup

  1. customA sealed tube equipped with a magnetic stirrer
  2. customThe mixture was then evaporated in vacuo
  3. extractionthe residue was extracted with Ethyl acetate (10 mL×2)
  4. extractionThe combined Ethyl acetate extract
  5. concentrationwas concentrated under reduced pressure
  6. customthe residue was purified with reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-7e17812fcf2f4df38ad4c3fe38363561
Source dataset
uspto-grants-2014_05
Patent number
US08722676B2

Reaction notes

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