Cyanoacetic acid → HCID 118390111, compound

HRID 1478014Notes

Reaction equation

HRID 1478014 reaction equation
[Cl:1][C:2]1[C:3]([NH:15][CH:16]2[CH2:24][CH2:23][CH:22]3[CH:18]([CH2:19][NH:20][CH2:21]3)[CH2:17]2)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=2)=[N:6][CH:7]=1.[C:25]([CH2:27][C:28](O)=[O:29])#[N:26].CCN=C=NCCCN(C)C.C1C=NC2N(O)N=NC=2C=1>C(Cl)Cl.CN(C=O)C>[Cl:1][C:2]1[C:3]([NH:15][CH:16]2[CH2:24][CH2:23][CH:22]3[CH:18]([CH2:19][N:20]([C:28](=[O:29])[CH2:27][C:25]#[N:26])[CH2:21]3)[CH2:17]2)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=2)=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 9740Cyanoacetic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 118390103HCID 118390103, compound

Product 1

HCID 118390111HCID 118390111, compoundYield 40.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 5-chloro-N2-(1-methyl-1H-pyrazol-4-yl)-N4-(octahydro-1H-isoindol-5-yl)pyrimidine-2,4-diamine (470 mg, 1.35 mmol), 2-cyanoacetic acid (246.7 mg, 2.90 mmol) in a mixture of DCM (40 mL) and DMF (10 mL) were added EDCI (505.2 mg, 2.64 mmol) and HOAT (325.4 mg, 0.30 mmol). After addition, the reaction mixture was stirred at 45° C. for 3 h, quenched with H2O (30 mL) and extracted with DCM (200 mL×3). The combined organic phases were washed with brine (200 mL), dried over anhydrous Na2SO4, then filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (DCM/MeOH (v/v)=50/1) to give the title compound as beige solid (228.4 mg, 40.8%).

Workup

  1. additionAfter addition
  2. customquenched with H2O (30 mL)
  3. extractionextracted with DCM (200 mL×3)
  4. washThe combined organic phases were washed with brine (200 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel column chromatography (DCM/MeOH (v/v)=50/1)

Sources & evidence

ORD record
ord-0deebd2db7a042a98b251c1413fbd03e
Source dataset
uspto-grants-2016_08
Patent number
US09403801B2

Reaction notes

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