Cesium carbonate → HCID 71559182, compound

HRID 1024015Notes

Reaction equation

HRID 1024015 reaction equation
Cl[C:2]1[CH:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:23][CH2:22][N:21]([CH:24]4[CH2:27][O:26][CH2:25]4)[CH2:20][CH2:19]3)=[CH:14][N:13]=2)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[CH:7]=1.C([O:31][CH2:32][C:33]1[C:38](B2OC(C)(C)C(C)(C)O2)=[CH:37][C:36]([F:48])=[CH:35][C:34]=1[N:49]1[CH2:61][CH2:60][N:52]2[C:53]3[CH2:54][CH2:55][CH2:56][CH2:57][C:58]=3[CH:59]=[C:51]2[C:50]1=[O:62])(=O)C.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.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:48][C:36]1[CH:37]=[C:38]([C:2]2[CH:3]=[C:4]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([N:18]4[CH2:23][CH2:22][N:21]([CH:24]5[CH2:27][O:26][CH2:25]5)[CH2:20][CH2:19]4)=[CH:14][N:13]=3)[C:5]3[N:6]([CH:8]=[CH:9][N:10]=3)[CH:7]=2)[C:33]([CH2:32][OH:31])=[C:34]([N:49]2[CH2:61][CH2:60][N:52]3[C:53]4[CH2:54][CH2:55][CH2:56][CH2:57][C:58]=4[CH:59]=[C:51]3[C:50]2=[O:62])[CH:35]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 75806TricyclohexylphosphineHCID 580442052-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-4-fluoro-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl AcetateHCID 86684122HCID 86684122, compound

Product 1

HCID 71559182HCID 71559182, compoundYield 11.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
140 °C

Procedure

To a solution of 102c (180 mg, 0.468 mol) in dioxane/H2O (12 mL/1 mL) was added 2-(5-fluoro-2-(hydroxymethyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-one 101l (225 mg, 0.468 mmol), Pd2(dba)3 (43 mg, 0.0468 mmol), tricyclohexylphosphine (131 mg, 0.468 mmol), and Cs2CO3 (305 mg, 0.935 mmol). This mixture was heated in microwave at 140° C. for 1 h. Then, the solid was filtered and the filtrate was concentrated to give a yellow solid, which was further purified by reverse-phase prep-HPLC to afford 102 as a white solid (36 mg, 11%). LCMS: [M+H]+ 663. 1H NMR (500 MHz, DMSO) δ 8.53 (d, J=2.5, 1H), 8.27 (s, 1H), 8.16 (s, 1H), 7.95 (s, 1H), 7.92-7.91 (d, J=2.5, 1H), 7.57 (s, 1H), 7.42-7.36 (m, 2H), 7.36-7.33 (m, 1H), 7.27-7.25 (d, J=9, 1H), 6.53 (s, 1H), 4.88-4.86 (t, J=9, 1H), 4.57-4.54 (m, 2H), 4.47-4.45 (m, 2H), 4.31-4.30 (d, J=4.5, 2H), 4.18-4.13 (m, 3H), 3.92-3.90 (m, 1H), 3.45-3.42 (m, 1H), 3.09-3.10 (m, 4H), 2.64-2.54 (m, 2H), 2.47-2.45 (m, 2H), 2.39-2.38 (m, 4H), 1.79-1.78 (m, 2H), 1.69-1.67 (m, 2H)

Workup

  1. filtrationThen, the solid was filtered
  2. concentrationthe filtrate was concentrated
  3. customto give a yellow solid, which
  4. customwas further purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-2afab01a642c45beb8ae25044c3f2ede
Source dataset
uspto-grants-2014_05
Patent number
US08722676B2

Reaction notes

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