Cesium carbonate → HCID 59606001, compound

HRID 1922839Notes

Reaction equation

HRID 1922839 reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:17][N:18]3[CH2:21][CH:20]([N:22]4[CH2:27][CH2:26][NH:25][C:24](=[O:28])[CH2:23]4)[CH2:19]3)[N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[C:4]([N:29]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)[N:3]=1.[CH2:35]([C:37]1[NH:38][C:39]2[CH:45]=[CH:44][CH:43]=[CH:42][C:40]=2[N:41]=1)[CH3:36].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]>[CH2:35]([C:37]1[N:38]([C:2]2[N:10]=[C:9]3[C:5]([N:6]=[C:7]([CH2:17][N:18]4[CH2:19][CH:20]([N:22]5[CH2:27][CH2:26][NH:25][C:24](=[O:28])[CH2:23]5)[CH2:21]4)[N:8]3[CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][O:12]3)=[C:4]([N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[N:3]=2)[C:39]2[CH:45]=[CH:44][CH:43]=[CH:42][C:40]=2[N:41]=1)[CH3:36]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 158072-EthylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596060104-{1-[2-Chloro-6-morpholin-4-yl-9-(tetrahydropyran-2-yl)-9H-purin-8-ylmethyl]azetidin-3-yl}piperazin-2-one

Product 1

HCID 59606001HCID 59606001, compoundYield 39.1%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
115 °C

Procedure

A mixture of 4-{1-[2-chloro-6-morpholin-4-yl-9-(tetrahydropyran-2-yl)-9H-purin-8-ylmethyl]azetidin-3-yl}piperazin-2-one (990 mg, 2.00 mmol), 2-ethylbenzimidazole (322 mg, 2.20 mmol), tris(dibenzylideneacetone)dipalladium (46 mg, 0.05 mmol), XPhos (95 mg, 0.20 mmol) and Cs2CO3 (980 mg, 3.01 mmol) in dioxane (30 mL) was purged with argon then heated at 115° C. for 6 h then stirred at r.t. for 16 h. The reaction mixture was filtered through Celite®, washing with dioxane, and the filtrate concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-10%) affording the title compound (470 mg, 39%). LCMS (method A): RT 2.01 and 1.92 min [M+H]+ 601.6

Workup

  1. customwas purged with argon
  2. filtrationThe reaction mixture was filtered through Celite®
  3. washwashing with dioxane
  4. concentrationthe filtrate concentrated in vacuo
  5. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-10%)

Sources & evidence

ORD record
ord-54390d571638455ab3646bd0ff7b5eb2
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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