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1,2-Ethanediamine, N1,N1,N2-trimethyl- → (2S,4S)-1-acryloyl-4-(4-amino-5-((3,5-dimethoxyphenyl)ethynyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-N-(2-(dimethylamino)ethyl)-N-methylpyrrolidine-2-carboxamide

HRID 516182
Notes
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Reaction equation

HRID 516182 reaction equation
[NH2:1][C:2]1[C:3]2[C:10]([C:11]#[C:12][C:13]3[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[C:15]([O:21][CH3:22])[CH:14]=3)=[CH:9][N:8]([C@@H:23]3[CH2:27][N:26]([C:28](OC(C)(C)C)=[O:29])[C@H:25]([C:35](O)=[O:36])[CH2:24]3)[C:4]=2[N:5]=[CH:6][N:7]=1.CN(C(ON1N=N[C:48]2C=CC=C[C:47]1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH3:60][N:61]([CH3:66])[CH2:62][CH2:63][NH:64][CH3:65].CCN(C(C)C)C(C)C>C(#N)C.O.C(OCC)(=O)C>[C:28]([N:26]1[CH2:27][C@@H:23]([N:8]2[C:4]3[N:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]=3[C:10]([C:11]#[C:12][C:13]3[CH:14]=[C:15]([O:21][CH3:22])[CH:16]=[C:17]([O:19][CH3:20])[CH:18]=3)=[CH:9]2)[CH2:24][C@H:25]1[C:35]([N:64]([CH2:63][CH2:62][N:61]([CH3:66])[CH3:60])[CH3:65])=[O:36])(=[O:29])[CH:47]=[CH2:48]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 673381,2-Ethanediamine, N1,N1,N2-trimethyl-HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 89870887(2S,4S)-4-(4-amino-5-((3,5-dimethoxyphenyl)ethynyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid

Product 1

HCID 90353248
(2S,4S)-1-acryloyl-4-(4-amino-5-((3,5-dimethoxyphenyl)ethynyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-N-(2-(dimethylamino)ethyl)-N-methylpyrrolidine-2-carboxamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (2S,4S)-4-(4-amino-5-((3,5-dimethoxyphenyl)ethynyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid (25.4 mg) obtained in Example 68 (Step 1), TBTU (17.7 mg), N,N,N′-trimethylethane-1,2-diamine (13 μl), and DIPEA (26 μl) in acetonitrile (3 ml) was stirred at room temperature for 1 hour. Ethyl acetate and water were added to separate the organic layer. The organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was purified by basic silica gel column chromatography (developing solvent: chloroform/methanol) to obtain the title compound as a light-yellow, amorphous substance (3 mg). Physical properties: m/z [M+H]+ 592.4

Workup

  1. customto separate the organic layer
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. distillationthe solvent was distilled off under reduced pressure
  4. customThe resulting residue was purified by basic silica gel column chromatography (developing solvent: chloroform/methanol)

Sources & evidence

ORD record
ord-f3fe99577fd64583923f4c9b2304dd92
Source dataset
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09108973B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes