Cesium carbonate → HCID 67492197, compound

HRID 1923250Notes

Reaction equation

HRID 1923250 reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][N:13]3[CH2:18][C@@H:17]4[CH2:19][C@H:14]3[CH2:15][N:16]4[S:20]([CH3:23])(=[O:22])=[O:21])[N:8]2[CH3:11])=[C:4]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[N:3]=1.[CH2:30]([C:32]1[NH:36][C:35]2[CH:37]=[CH:38][CH:39]=[CH:40][C:34]=2[N:33]=1)[CH3:31].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]>[CH2:30]([C:32]1[N:33]([C:2]2[N:10]=[C:9]3[C:5]([N:6]=[C:7]([CH2:12][N:13]4[CH2:18][C@@H:17]5[CH2:19][C@H:14]4[CH2:15][N:16]5[S:20]([CH3:23])(=[O:21])=[O:22])[N:8]3[CH3:11])=[C:4]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[N:3]=2)[C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=1)[CH3:31]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 158072-EthylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86648238HCID 86648238, compound

Product 1

HCID 67492197HCID 67492197, compoundYield 82%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of 2-chloro-8-((1S,4S)-5-methanesulfonyl-2,5-diazabicyclo[2.2.1]hept-2-ylmethyl)-9-methyl-6-morpholin-4-yl-9H-purine (150 mg, 0.34 mmol), 2-ethyl-1H-benzoimidazole (59 mg, 0.40 mmol), Pd2dba3 (9 mg, 0.009 mmol), Xphos (18 mg, 0.036 mmol) and cesium carbonate (165 mg, 0.51 mmol) in 1,4-dioxane (3 mL) was purged with argon gas then subjected to microwave irradiation at 150° C. for 30 min. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge (10 g), which was washed with MeOH/DCM before the desired product was eluted with 2 M NH3 in MeOH/DCM. The product was collected and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, EtOAc:MeOH 100:0 to 99:1 to 98:2) to afford 553 as a white solid (153 mg, 82%). LCMS (Method I): RT=2.53 min, M+H+=552. 1H NMR (CDC3, 400 MHz) δ 8.01 (m, 1 H); 7.77 (m, 1 H); 7.28 (m, 2 H); 4.35 (m, 5 H); 4.06 (d, J=13.6 Hz, 1 H); 3.96 (d, J=13.6 Hz, 1 H); 3.87 (m, 7 H); 3.65 (d, J=9.5 Hz, 1 H); 3.61 (bs, 1 H); 3.37 (q, J=7.5 Hz, 2 H); 3.27 (dd, J=9.5, 2.3 Hz, 1 H); 3.02-2.93 (m, 2 H); 2.91 (s, 3 H); 1.99 (d, J=10.2 Hz, 1 H); 1.79 (d, J=10.2 Hz, 1 H) and 1.45 (t, J=7.5 Hz, 3 H)

Workup

  1. customwas purged with argon gas
  2. customirradiation at 150° C. for 30 min
  3. washwas washed with MeOH/DCM before the desired product
  4. washwas eluted with 2 M NH3 in MeOH/DCM
  5. customThe product was collected
  6. concentrationconcentrated in vacuo
  7. customThe resultant residue was purified by flash chromatography (Si—PPC, EtOAc:MeOH 100:0 to 99:1 to 98:2)

Sources & evidence

ORD record
ord-07807265b94340d5a57ecf91c94affaa
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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