O-Phenylenediamine → N-[9-methyl-6-morpholin-4-yl-8-(4-oxetan-3-ylpiperidin-1-ylmethyl)-9H-purin-2-yl]benzene-1,2-diamine

HRID 1945635Notes

Reaction equation

HRID 1945635 reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][N:13]3[CH2:18][CH2:17][CH:16]([CH:19]4[CH2:22][O:21][CH2:20]4)[CH2:15][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.[C:29]1([NH2:36])[C:30]([NH2:35])=[CH:31][CH:32]=[CH:33][CH: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+]>CN(C=O)C.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][CH2:15][CH:16]([CH:19]3[CH2:20][O:21][CH2:22]3)[CH2:17][CH2:18]2)=[N:6][C:5]2[C:9]1=[N:10][C:2]([NH:35][C:30]1[C:29]([NH2:36])=[CH:34][CH:33]=[CH:32][CH:31]=1)=[N:3][C:4]=2[N:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1

Participants

7

Reactant 4

HCID 7243O-PhenylenediamineHCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596054062-Chloro-9-methyl-6-morpholin-4-yl-8-(4-oxetan-3-ylpiperidin-1-ylmethyl)-9H-purine

Product 1

HCID 59605317N-[9-methyl-6-morpholin-4-yl-8-(4-oxetan-3-ylpiperidin-1-ylmethyl)-9H-purin-2-yl]benzene-1,2-diamineYield 50%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-chloro-9-methyl-6-morpholin-4-yl-8-(4-oxetan-3-yl-piperidin-1-ylmethyl)-9H-purine (0.2 g, 0.49 mmol), benzene-1,2-diamine (0.106 g, 0.98 mmol), Xphos (0.047 g, 0.098 mmol), Pd2(dba)3 (0.022 g, 0.025 mmol) and Cs2CO3 (0.32 g, 0.98 mmol) in DMF (2 mL) was subjected to microwave irradiation at 150° C. for 30 min. The suspension was filtered through Celite and the solution was concentrated in vacuo. The residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 10:90) to give N-[9-Methyl-6-morpholin-4-yl-8-(4-oxetan-3-yl-piperidin-1-ylmethyl)-9H-purin-2-yl]benzene-1,2-diamine as yellow foam (0.117 g, 50%). LCMS (Method A): RT=2.14 min, [M+H]+ 479.2

Workup

  1. customirradiation at 150° C. for 30 min
  2. filtrationThe suspension was filtered through Celite
  3. concentrationthe solution was concentrated in vacuo
  4. customThe residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 10:90)

Sources & evidence

ORD record
ord-71c0ae989f3843fcb3e7052c8d75477d
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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