Cyanoacetic acid → 3-(9-((5-chloro-2-((1-methyl-1H-imidazol-4-yl)amino)pyrimidin-4-yl)amino)-3-azaspiro[5.5]undecan-3-yl)-3-oxopropanenitrile

HRID 1478049Notes

Reaction equation

HRID 1478049 reaction equation
Cl.[CH2:2]1[C:7]2([CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH2:6][CH2:5][CH:4]([NH:13][C:14]2[C:19]([Cl:20])=[CH:18][N:17]=[C:16]([NH:21][C:22]3[N:23]=[CH:24][N:25]([CH3:27])[CH:26]=3)[N:15]=2)[CH2:3]1.[C:28]([CH2:30][C:31](O)=[O:32])#[N:29].C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>C(Cl)Cl.CN(C=O)C>[Cl:20][C:19]1[C:14]([NH:13][CH:4]2[CH2:5][CH2:6][C:7]3([CH2:8][CH2:9][N:10]([C:31](=[O:32])[CH2:30][C:28]#[N:29])[CH2:11][CH2:12]3)[CH2:2][CH2:3]2)=[N:15][C:16]([NH:21][C:22]2[N:23]=[CH:24][N:25]([CH3:27])[CH:26]=2)=[N:17][CH:18]=1

Participants

7

Reactant 4

HCID 9740Cyanoacetic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 118390036N4-(9-azaspiro[5.5]undecan-3-yl)-5-chloro-N2-(1-methylimidazol-4-yl)pyrimidine-2,4-diamine hydrochloride

Product 1

HCID 1183901003-(9-((5-chloro-2-((1-methyl-1H-imidazol-4-yl)amino)pyrimidin-4-yl)amino)-3-azaspiro[5.5]undecan-3-yl)-3-oxopropanenitrileYield 28.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of N4-(9-azaspiro[5.5]undecan-3-yl)-5-chloro-N2-(1-methylimidazol-4-yl)pyrimidine-2,4-diamine hydrochloride (200 mg, 0.4850 mmol), 2-cyanoacetic acid (41.6 mg, 0.489 mmol) and TEA (98.4 mg, 0.972 mmol) in a mixture of DCM and DMF (8 mL/2 mL) were added HOAT (99.6 mg, 0.732 mmol) and EDCI (138.7 mg, 0.724 mmol). The reaction was stirred for 2 h and concentrated in vacuo. The residue was purified by silica gel column chromatography (DCM/MeOH (v/v)=30/1) to give the title compound as a light yellow solid (61.8 mg, 28.8%).

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was purified by silica gel column chromatography (DCM/MeOH (v/v)=30/1)

Sources & evidence

ORD record
ord-d9d4d173a70040ee95af626c6f607cdd
Source dataset
uspto-grants-2016_08
Patent number
US09403801B2

Reaction notes

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