Cyanoacetic acid → HCID 118390080, compound

HRID 1478057Notes

Reaction equation

HRID 1478057 reaction equation
[Cl:1][C:2]1[C:3]([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:4][C:5]([NH:8][C:9]2[CH:10]=[N:11][N:12]([CH2:14][CH:15]3[CH2:17][CH2:16]3)[CH:13]=2)=[N:6][CH:7]=1.[C:30]([CH2:32][C:33](O)=[O:34])#[N:31].C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>ClCCl.CN(C)C=O.O>[Cl:1][C:2]1[C:3]([NH:18][CH:19]2[CH2:20][CH2:21][C:22]3([CH2:23][CH2:24][N:25]([C:33](=[O:34])[CH2:32][C:30]#[N:31])[CH2:26][CH2:27]3)[CH2:28][CH2:29]2)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[N:11][N:12]([CH2:14][CH:15]3[CH2:17][CH2:16]3)[CH:13]=2)=[N:6][CH:7]=1

Participants

8

Reactant 4

HCID 9740Cyanoacetic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 118390051HCID 118390051, compound

Product 1

HCID 118390080HCID 118390080, compoundYield 45.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-chloro-N2-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)-N4-(3-azaspiro[5.5]undecan-9-yl)pyrimidine-2,4-diamine (300.5 mg, 0.72 mmol), 2-cyanoacetic acid (92.2 mg, 1.08 mmol), HOAT (196.5 mg, 1.44 mmol) and EDCI (276.5 mg, 1.44 mmol) in a mixture of dichloromethane (20 mL) and N,N-dimethylformamide (5 mL) was added TEA (146.2 mg, 1.45 mmol). The mixture was stirred at room temperature for 1 h then diluted with water (50 mL), and extracted with DCM/MeOH (10/1, 50 mL×3). The combined organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (DCM/MeOH (v/v)=100/1) to give the product as a yellow solid (156.8 mg, 44.94%).

Workup

  1. extractionextracted with DCM/MeOH (10/1, 50 mL×3)
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel column chromatography (DCM/MeOH (v/v)=100/1)

Sources & evidence

ORD record
ord-32714c45fd8641079bd2f1dde4d07d27
Source dataset
uspto-grants-2016_08
Patent number
US09403801B2

Reaction notes

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