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1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → N-{2-[4-({3-chloro-4-[3-(trifluoromethoxy)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]ethyl}-2-(methylsulfonyl)acetamide

HRID 1926073
Notes
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Reaction equation

HRID 1926073 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]([O:29][C:30]([F:33])([F:32])[F:31])[CH:24]=4)=[C:18]([Cl:34])[CH:17]=3)=[N:12][CH:11]=[N:10][C:9]=2[CH:8]=[CH:7]1.[CH3:35][S:36]([CH2:39][C:40](O)=[O:41])(=[O:38])=[O:37].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1>O.CN(C)C=O.C(N(CC)CC)C>[Cl:34][C:18]1[CH:17]=[C:16]([NH:15][C:13]2[C:14]3[N:6]([CH2:5][CH2:4][NH:3][C:40](=[O:41])[CH2:39][S:36]([CH3:35])(=[O:38])=[O:37])[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]([O:29][C:30]([F:33])([F:32])[F:31])[CH:24]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 37328412-Methanesulfonylacetic acidHCID 866157705-(2-aminoethyl)-N-{3-chloro-4-[3-(trifluoromethoxy)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidin-4-amine dihydrochloride

Product 1

HCID 57597390
N-{2-[4-({3-chloro-4-[3-(trifluoromethoxy)phenoxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl]ethyl}-2-(methylsulfonyl)acetamide
Yield 64.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of 5-(2-aminoethyl)-N-{3-chloro-4-[3-(trifluoromethoxy)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidin-4-amine dihydrochloride (160 mg), 2-(methylsulfonyl)acetic acid (82.3 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (171 mg), 1-hydroxybenzotriazole monohydrate (137 mg), triethylamine (0.42 mL) and N,N-dimethylformamide (5.0 mL) was stirred at room temperature for 20 hrs. Water was added to the reaction system and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried over magnesium sulfate. After concentration under reduced pressure, the residue was separated and purified by basic silica gel column chromatography (eluent, ethyl acetate→ethyl acetate:methanol=4:1) and crystallization from ethanol-ethyl acetate-diisopropyl ether to give the title compound (112 mg) as pale-yellow crystals.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water and saturated brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationAfter concentration under reduced pressure
  5. customthe residue was separated
  6. custompurified by basic silica gel column chromatography (eluent, ethyl acetate→ethyl acetate:methanol=4:1) and crystallization from ethanol-ethyl acetate-diisopropyl ether

Sources & evidence

ORD record
ord-6d42f181c9fd417197af4129a5af437f
Source dataset
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08178543B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes