Cyanoacetic acid → HCID 118390057, compound

HRID 1478067Notes

Reaction equation

HRID 1478067 reaction equation
Cl.[Cl:2][C:3]1[C:4]([NH:18][CH:19]2[CH2:29][CH2:28][C:22]3([CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)[CH2:21][CH2:20]2)=[N:5][C:6]([NH:9][C:10]2[CH:14]=[C:13]([CH:15]3[CH2:17][CH2:16]3)[NH:12][N:11]=2)=[N:7][CH:8]=1.[C:30]([CH2:32][C:33](O)=[O:34])#[N:31].C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>C(Cl)Cl.CN(C=O)C>[Cl:2][C:3]1[C:4]([NH:18][CH:19]2[CH2:29][CH2:28][C:22]3([CH2:27][CH2:26][N:25]([C:33](=[O:34])[CH2:32][C:30]#[N:31])[CH2:24][CH2:23]3)[CH2:21][CH2:20]2)=[N:5][C:6]([NH:9][C:10]2[CH:14]=[C:13]([CH:15]3[CH2:17][CH2:16]3)[NH:12][N:11]=2)=[N:7][CH:8]=1

Participants

7

Reactant 4

HCID 9740Cyanoacetic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 118390062HCID 118390062, compound

Product 1

HCID 118390057HCID 118390057, compoundYield 36.91%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-chloro-N2-(5-cyclopropyl-1H-pyrazol-3-yl)-N4-(3-azaspiro[5.5]undecan-9-yl)pyrimidine-2,4-diamine hydrochloride (270 mg, 0.6159 mmol) in a mixture of DCM and DMF (6 mL/2 mL) were added TEA (253.2 mg, 2.502 mmol), cyanoacetic acid (52.1 mg, 0.733 mmol), HOAT (124.8 mg, 0.9169 mmol) and EDCI (177.5 mg, 0.9259 mmol). The reaction mixture was stirred at rt for 1.5 h then quenched with water (30 mL), and extracted with DCM/MeOH (10/1, 80 mL×3). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated in vacuo and the residue was purified by silica gel column chromatography (DCM/MeOH (v/v)=30/1). The crude product was recrystallized from MeOH (10 mL) to give the title compound as a white solid (106.6 mg, 36.91%).

Workup

  1. customthen quenched with water (30 mL)
  2. extractionextracted with DCM/MeOH (10/1, 80 mL×3)
  3. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customthe residue was purified by silica gel column chromatography (DCM/MeOH (v/v)=30/1)
  7. customThe crude product was recrystallized from MeOH (10 mL)

Sources & evidence

ORD record
ord-69d59bd28e8646d0be440a2fbc09e097
Source dataset
uspto-grants-2016_08
Patent number
US09403801B2

Reaction notes

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