Cesium carbonate → HCID 59605304, compound

HRID 1945989Notes

Reaction equation

HRID 1945989 reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][N:13]3[CH2:16][CH:15]([CH:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)[CH2:14]3)[N:8]2[CH3:11])=[C:4]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[N:3]=1.[CH3:29][C:30]1[NH:31][C:32]2[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=2[N:34]=1.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]>[CH3:11][N:8]1[C:7]([CH2:12][N:13]2[CH2:14][CH:15]([CH:17]3[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)[CH2:16]2)=[N:6][C:5]2[C:9]1=[N:10][C:2]([N:31]1[C:32]3[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=3[N:34]=[C:30]1[CH3:29])=[N:3][C:4]=2[N:23]1[CH2:24][CH2:25][O:26][CH2:27][CH2:28]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 119842-MethylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 59605752HCID 59605752, compound

Product 1

HCID 59605304HCID 59605304, compoundYield 75%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
150 °C

Procedure

A mixture of 2-chloro-9-methyl-6-morpholin-4-yl-8-[3-(tetrahydropyran-4-yl)azetidin-1-ylmethyl]-9H-purine (112 mg, 0.28 mmol), 2-methylbenzimidazole (44 mg, 0.33 mmol), tris(dibenzylideneacetone)dipalladium (13 mg, 0.01 mmol), Xphos (26 mg, 0.06 mmol) and Cs2CO3 (179 mg, 0.55 mmol) in dioxane (3 mL) was purged with argon then heated at 150° C. for 30 min in a microwave reactor. The reaction mixture was filtered through a pad of celite, washing with EtOAc. The filtrate was concentrated in vacuo and purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%) affording 467 as a cream solid (105 mg, 75%). LCMS (Method I): RT 2.46 min, [M+H]+ 503.2. 1H NMR (CDCl3, 400 MHz): δ 8.10-8.05 (m, 1 H); 7.73-7.67 (m, 1 H); 7.28-7.23 (m, 2 H); 4.35 (m, 4 H); 3.97 (dd, J=11.4, 4.1 Hz, 2 H); 3.89-3.82 (m, 9 H); 3.54 (m, 2 H); 3.37 (td, J=11.4, 2.0 Hz, 2 H); 3.06 (m, 2 H); 2.94 (s, 3 H); 2.38-2.27 (m, 1 H); 1.54 (m, 2 H) and 1.32-1.14 (m, 3 H)

Workup

  1. customwas purged with argon
  2. filtrationThe reaction mixture was filtered through a pad of celite
  3. washwashing with EtOAc
  4. concentrationThe filtrate was concentrated in vacuo
  5. custompurified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%)

Sources & evidence

ORD record
ord-122852ee800243c6b64c5ecf5297a968
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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