Glycolic Acid → 2-(4-{2-(2-Aminopyrimidin-5-yl)-9-isobutyl-6-[(3S)-3-methylmorpholin-4-yl]-9H-purin-8-yl}piperazin-1-yl)-2-oxoethanol

HRID 421440Notes

Reaction equation

HRID 421440 reaction equation
[CH2:1]([N:5]1[C:13]([N:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[N:12][C:11]2[C:6]1=[N:7][C:8]([C:27]1[CH:28]=[N:29][C:30]([NH2:33])=[N:31][CH:32]=1)=[N:9][C:10]=2[N:20]1[CH2:25][CH2:24][O:23][CH2:22][C@@H:21]1[CH3:26])[CH:2]([CH3:4])[CH3:3].[OH:34][CH2:35][C:36](O)=[O:37].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>CCOCC.C(Cl)(Cl)Cl.C(Cl)Cl>[NH2:33][C:30]1[N:31]=[CH:32][C:27]([C:8]2[N:7]=[C:6]3[C:11]([N:12]=[C:13]([N:14]4[CH2:19][CH2:18][N:17]([C:35](=[O:34])[CH2:36][OH:37])[CH2:16][CH2:15]4)[N:5]3[CH2:1][CH:2]([CH3:4])[CH3:3])=[C:10]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][C@@H:21]3[CH3:26])[N:9]=2)=[CH:28][N:29]=1

Participants

10

Reactant 6

HCID 757Glycolic AcidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 593335555-{9-Isobutyl-6-[(3S)-3-methylmorpholin-4-yl]-8-piperazin-1-yl-9H-purin-2-yl}pyrimidin-2-amine

Product 1

HCID 593335712-(4-{2-(2-Aminopyrimidin-5-yl)-9-isobutyl-6-[(3S)-3-methylmorpholin-4-yl]-9H-purin-8-yl}piperazin-1-yl)-2-oxoethanolYield 77%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

A methylene chloride (5 ml) solution of 5-{9-isobutyl-6-[(3S)-3-methylmorpholin-4-yl]-8-piperazin-1-yl-9H-purin-2-yl}pyrimidin-2-amine (126 mg, 0.28 mmol), hydroxyacetic acid (25 mg, 0.33 mmol), 1-hydroxybenzotriazole (37 mg, 0.28 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (64 mg, 0.33 mmol), and triethylamine (58 μl, 0.42 mmol) was stirred at room temperature for 2 days. Chloroform and saturated aqueous sodium hydrogen carbonate solution were added to the reaction mixture and the resulting mixture was extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate and, after filtration, the filtrate was concentrated under reduced pressure. The residue was purified by flash silica gel column chromatography (methylene chloride:methanol=96:4) to give a solid. Ether was added to the resulting solid and the solid was collected by filtration and dried to give the title compound (110 mg, 77%) as a powder.

Workup

  1. extractionthe resulting mixture was extracted with chloroform
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. filtrationafter filtration
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by flash silica gel column chromatography (methylene chloride:methanol=96:4)
  6. customto give a solid
  7. filtrationthe solid was collected by filtration
  8. customdried

Sources & evidence

ORD record
ord-3f1457db96cd4eadac635370f6b31ede
Source dataset
uspto-grants-2012_01
Patent number
US08097622B2

Reaction notes

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