Cyanoacetic acid → HCID 118390071, compound

HRID 1478063Notes

Reaction equation

HRID 1478063 reaction equation
Cl[C:2]1[C:3]([NH:17][CH:18]2[CH2:25][CH:21]3[CH2:22][NH:23][CH2:24][CH:20]3[CH2:19]2)=[N:4][C:5]([NH:8][C:9]2[CH:13]=[C:12]([CH:14]3[CH2:16][CH2:15]3)[NH:11][N:10]=2)=[N:6][CH:7]=1.C(C[C:29](O)=[O:30])#N.CCN=C=[N:36][CH2:37][CH2:38][CH2:39]N(C)C.C1C=NC2N([OH:52])N=NC=2C=1>C(Cl)Cl.CN(C=O)C>[CH:14]1([C:12]2[NH:11][N:10]=[C:9]([NH:8][C:5]3[N:4]=[C:3]([NH:17][CH:18]4[CH2:25][CH:21]5[CH2:22][N:23]([C:39](=[O:52])[CH2:38][C:37]#[N:36])[CH2:24][CH:20]5[CH2:19]4)[C:2]([O:30][CH3:29])=[CH:7][N:6]=3)[CH:13]=2)[CH2:16][CH2:15]1

Participants

7

Reactant 4

HCID 9740Cyanoacetic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 118390021HCID 118390021, compound

Product 1

HCID 118390071HCID 118390071, compoundYield 100.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-chloro-N2-(5-cyclopropyl-1H-pyrazol-3-yl)-N4-(octahydrocyclopenta[c]pyrrol-5-yl)pyrimidine-2,4-diamine (240.0 mg, 0.67 mmol) and 2-cyanoacetic acid (107.7 mg, 1.27 mmol) in a mixture of DCM (20 mL) and DMF (5 mL) were added EDCI (311.4 mg, 1.61 mmol) and HOAT (186.3 mg, 1.37 mmol). The reaction mixture was stirred at rt for 1 h and then quenched with H2O (30 mL) and extracted with DCM (100 mL×3). The combined organic phases were washed with brine (100 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (MeOH/DCM (v/v)=1/20) and a preparative HPLC to give the title compound as a beige solid (284.7 mg, 100%).

Workup

  1. customquenched with H2O (30 mL)
  2. extractionextracted with DCM (100 mL×3)
  3. washThe combined organic phases were washed with brine (100 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography (MeOH/DCM (v/v)=1/20)

Sources & evidence

ORD record
ord-252c87f675c643238ca6e82deb95948f
Source dataset
uspto-grants-2016_08
Patent number
US09403801B2

Reaction notes

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