Cesium carbonate → HCID 59605506, compound

HRID 1945980Notes

Reaction equation

HRID 1945980 reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][CH2:13][N:14]3[CH2:17][C:16]([CH3:19])([OH:18])[CH2:15]3)[N:8]2[CH3:11])=[C:4]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[N:3]=1.[CH2:26]([C:28]1[NH:29][C:30]2[CH:36]=[CH:35][CH:34]=[CH:33][C:31]=2[N:32]=1)[CH3:27].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Cs+].[Cs+]>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]>[CH2:26]([C:28]1[N:29]([C:2]2[N:10]=[C:9]3[C:5]([N:6]=[C:7]([CH2:12][CH2:13][N:14]4[CH2:15][C:16]([CH3:19])([OH:18])[CH2:17]4)[N:8]3[CH3:11])=[C:4]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[N:3]=2)[C:30]2[CH:36]=[CH:35][CH:34]=[CH:33][C:31]=2[N:32]=1)[CH3:27]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 158072-EthylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 59606149HCID 59606149, compound

Product 1

HCID 59605506HCID 59605506, compoundYield 74%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

A mixture of 1-[2-(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)ethyl]-3-methylazetidin-3-ol (80 mg, 0.22 mmol), 2-ethylbenzimidazole (35 mg, 0.24 mmol), Pd2(dba)3 (5 mg, 2.5 mol %), Xphos (10.4 mg, 10 mol %) and Cs2CO3 (107 mg, 0.33 mmol) in dioxane (2.0 mL) was purged with argon gas then heated at 120° C., for 19 h, in a sealed tube. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH then the desired product eluted with 2 M NH3 in MeOH. The resulting residue was purified by flash chromatography (Si—PCC, 0-10% 2 M NH3/MeOH in DCM) to give 458 (77 mg, 74%) as a pale beige solid. LCMS: (Method I): RT 2.39 min; [M+H]+ 477.2. 1H NMR (400 MHz, CHCl3-d): δ 8.01-7.96 (m, 1 H), 7.76-7.72 (m, 1 H), 7.26-7.22 (m, 2 H), 4.45-4.32 (m, 4 H), 3.86 (t, J=4.8 Hz, 4 H), 3.77 (s, 3 H), 3.40 (d, J=7.3 Hz, 2 H), 3.34 (q, J=7.5 Hz, 2 H), 3.14 (d, J=7.3 Hz, 2 H), 3.02 (t, J=7.3 Hz, 3 H), 2.92 (t, J=7.3 Hz, 2 H), 1.53 (s, 3 H), 1.44 (t, J=7.5 Hz, 3 H)

Workup

  1. customwas purged with argon gas
  2. washwashed with MeOH
  3. washthe desired product eluted with 2 M NH3 in MeOH
  4. customThe resulting residue was purified by flash chromatography (Si—PCC, 0-10% 2 M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-200ee0d4746d418486d0bc7f358dd2a2
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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