1-Hydroxybenzotriazole → N-[2-(4-{[3-chloro-4-(3-chlorophenoxy)phenyl]amino}-5H-pyrrolo[3,2-d]pyrimidin-5-yl)ethyl]-2-(methylsulfonyl)acetamide

HRID 1926104Notes

Reaction equation

HRID 1926104 reaction equation
Cl.Cl.[NH2:3][CH2:4][CH2:5][N:6]1[C:14]2[C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=4)=[C:18]([Cl:30])[CH:17]=3)=[N:12][CH:11]=[N:10][C:9]=2[CH:8]=[CH:7]1.[CH3:31][S:32]([CH2:35][C:36](O)=[O:37])(=[O:34])=[O:33].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.O.C(N(CC)CC)C>[Cl:30][C:18]1[CH:17]=[C:16]([NH:15][C:13]2[C:14]3[N:6]([CH2:5][CH2:4][NH:3][C:36](=[O:37])[CH2:35][S:32]([CH3:31])(=[O:34])=[O:33])[CH:7]=[CH:8][C:9]=3[N:10]=[CH:11][N:12]=2)[CH:21]=[CH:20][C:19]=1[O:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 37328412-Methanesulfonylacetic acidHCID 675207235-(2-aminoethyl)-N-[3-chloro-4-(3-chlorophenoxy)phenyl]-5H-pyrrolo[3,2-d]pyrimidin-4-amine dihydrochloride

Product 1

HCID 11678194N-[2-(4-{[3-chloro-4-(3-chlorophenoxy)phenyl]amino}-5H-pyrrolo[3,2-d]pyrimidin-5-yl)ethyl]-2-(methylsulfonyl)acetamideYield 68.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a solution of 5-(2-aminoethyl)-N-[3-chloro-4-(3-chlorophenoxy)phenyl]-5H-pyrrolo[3,2-d]pyrimidin-4-amine dihydrochloride (200 mg), 2-(methylsulfonyl)acetic acid (113 mg) and 1-hydroxybenzotriazole (122 mg) in N,N-dimethylformamide (5.0 mL) were added a solution of triethylamine (419 mg) in N,N-dimethylformamide (1.25 mL) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (173 mg) under ice-cooling. After stirring the reaction mixture at room temperature for 16 hrs, water was added under ice-cooling, and the mixture was extracted twice with ethyl acetate. The organic layers were collected, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (eluent:ethyl acetate/methanol=100/0→80/20), and recrystallized from ethanol-ethyl acetate-diisopropyl ether to give the title compound (151 mg) as crystals.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. extractionthe mixture was extracted twice with ethyl acetate
  4. customThe organic layers were collected
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column chromatography (eluent:ethyl acetate/methanol=100/0→80/20)
  8. customrecrystallized from ethanol-ethyl acetate-diisopropyl ether

Sources & evidence

ORD record
ord-51aea045a27c4f0b8f097e06193f80d1
Source dataset
uspto-grants-2012_05
Patent number
US08178543B2

Reaction notes

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