Cesium carbonate → HCID 59605634, compound

HRID 1923313Notes

Reaction equation

HRID 1923313 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[C:5]2[N:10]=[C:9]([CH2:11][C:12]([N:14]3[CH2:19][CH2:18][N:17]([C:20]([CH3:24])([CH3:23])[CH2:21][OH:22])[CH2:16][CH2:15]3)=[O:13])[S:8][C:6]=2[N:7]=1.[CH2:31]([C:33]1[NH:34][C:35]2[CH:41]=[CH:40][CH:39]=[CH:38][C:36]=2[N:37]=1)[CH3:32].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]>[CH2:31]([C:33]1[N:34]([C:2]2[N:3]=[C:4]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[C:5]3[N:10]=[C:9]([CH2:11][C:12]([N:14]4[CH2:15][CH2:16][N:17]([C:20]([CH3:23])([CH3:24])[CH2:21][OH:22])[CH2:18][CH2:19]4)=[O:13])[S:8][C:6]=3[N:7]=2)[C:35]2[CH:41]=[CH:40][CH:39]=[CH:38][C:36]=2[N:37]=1)[CH3:32]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 158072-EthylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 59605655HCID 59605655, compound

Product 1

HCID 59605634HCID 59605634, compoundYield 17.7%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

A mixture of 2-(5-chloro-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-yl)-1-[4-(2-hydroxy-1,1-dimethylethyl)piperazin-1-yl]ethanone (65 mg, 0.14 mmol), 2-ethylbenzimidazole (23 mg, 0.16 mmol), tris(dibenzylideneacetone)dipalladium (4 mg, 2.5 mol %), XPhos (7 mg, 10 mol %) and Cs2CO3 (70 mg, 0.21 mmol) in dioxane (2 mL) was purged with argon then heated at 110° C. for 24 h in a sealed tube. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH/DCM. The resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-10%) followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 20 nM NEt3 in water on a gradient acetonitrile 10-95%) affording 712 as a yellow solid (14 mg, 17%). LCMS (method I): RT 2.58 min, [M+H]+ 565.2. 1H NMR (CDCl3, 400 MHz): δ 8.01-7.98 (1 H, m), 7.76-7.75 (1 H, m), 7.29-7.29 (2 H, m), 4.41 (4 H, s), 4.18 (2 H, s), 3.93-3.75 (9 H, m), 3.56 (2 H, brd s), 3.34 (2 H, q, J=7.47 Hz), 2.90-2.70 (4 H, brd m), 1.43 (3 H, t, J=7.47 Hz), 1.23-1.21 (6 H, m)

Workup

  1. customwas purged with argon
  2. washwas washed with MeOH
  3. washthe product eluted with 2M NH3/MeOH/DCM
  4. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-10%)

Sources & evidence

ORD record
ord-846d7b35e82e4ab18e7ba5cc4138e78b
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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