Cesium carbonate → HCID 59605899, compound

HRID 1923111Notes

Reaction equation

HRID 1923111 reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][CH2:13][N:14]3[CH2:19][CH2:18][O:17][C:16]([CH3:21])([CH3:20])[CH2:15]3)[N:8]2[CH3:11])=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[N:3]=1.[CH2:28]([C:30]1[NH:31][C:32]2[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=2[N:34]=1)[CH3:29].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]>[CH2:28]([C:30]1[N:31]([C:2]2[N:10]=[C:9]3[C:5]([N:6]=[C:7]([CH2:12][CH2:13][N:14]4[CH2:19][CH2:18][O:17][C:16]([CH3:21])([CH3:20])[CH2:15]4)[N:8]3[CH3:11])=[C:4]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)[N:3]=2)[C:32]2[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=2[N:34]=1)[CH3:29]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 158072-EthylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596055772-Chloro-8-[2-(2,2-dimethylmorpholin-4-yl)ethyl]-9-methyl-6-morpholin-4-yl-9H-purine

Product 1

HCID 59605899HCID 59605899, compoundYield 65.1%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

A mixture of 2-chloro-8-[2-(2,2-dimethylmorpholin-4-yl)ethyl]-9-methyl-6-morpholin-4-yl-9H-purine (57 mg, 0.14 mmol), 2-ethylbenzimidazole (23 mg, 0.16 mmol), Pd2(dba)3 (3.3 mg, 2.5 mol %), Xphos (6.9 mg, 10 mol %) and Cs2CO3 (71 mg, 0.27 mmol) in dioxane (1 0 mL) was purged with argon gas then heated at 120° C., for 16 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, 0-5% MeOH in DCM) to give 392 (46 mg, 63%) as a pale yellow solid. LCMS: (Method G): RT 6.31 min; [M+H]+ 505.3. 1H NMR (400 MHz, CHCl3-d): δ 8.02-7.97 (m, 1 H), 7.78-7.72 (m, 1 H), 7.27-7.22 (m, 2 H), 4.48-4.20 (m, 4 H), 3.89-3.83 (m, 4 H), 3.79 (s, 3 H), 3.77-3.55 (m, 2 H), 3.35 (q, J=7.5 Hz, 2 H), 3.12-2.97 (m, 2 H), 2.91-2.76 (m, 2 H), 2.57-2.43 (m, 2 H), 2.42-2.29 (m, 2 H), 1.44 (t, J=7.5 Hz, 3 H), 1.26 (s, 6 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, 0-5% MeOH in DCM)

Sources & evidence

ORD record
ord-373f97b2cf054c0196163428f3a1b72c
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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