Triethylamine → 3-(5-((5-chloro-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)amino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-3-oxopropanenitrile

HRID 1477987Notes

Reaction equation

HRID 1477987 reaction equation
[Cl:1][C:2]1[C:3]([NH:15][CH:16]2[CH2:23][CH:19]3[CH2:20][NH:21][CH2:22][CH:18]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:24]([CH2:26][C:27](O)=[O:28])#[N:25].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC>C(Cl)Cl.CN(C=O)C>[Cl:1][C:2]1[C:3]([NH:15][CH:16]2[CH2:23][CH:19]3[CH2:20][N:21]([C:27](=[O:28])[CH2:26][C:24]#[N:25])[CH2:22][CH:18]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 8471TriethylamineHCID 9740Cyanoacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 1183899865-chloro-N2-(1-methyl-1H-pyrazol-4-yl)-N4 (octahydrocyclopenta[c]pyrrol-5-yl)pyrimidine-2,4-diamine

Product 1

HCID 1183901193-(5-((5-chloro-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)amino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-3-oxopropanenitrileYield 72.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-chloro-N2-(1-methyl-1H-pyrazol-4-yl)-N4-(octahydrocyclopenta[c]pyrrol-5-yl)pyrimidine-2,4-diamine (401.6 mg, 1.20 mmol), 2-cyanoacetic acid (110.3 mg, 1.30 mmol) in a mixture of DCM and DMF (4/1 (v/v)), 50 mL) were added HATU (555.6 mg, 1.46 mmol) and Et3N (375.6 mg, 3.71 mmol). The reaction mixture was stirred at rt overnight, 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, concentrated in vacuo. The residue was purified by silica gel column chromatography (DCM/MeOH (v/v)=50/1) to give the title compound as a beige solid (350 mg, 72.8%).

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. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel column chromatography (DCM/MeOH (v/v)=50/1)

Sources & evidence

ORD record
ord-875880650cdd4e0ca2a3d1b5778e9e62
Source dataset
uspto-grants-2016_08
Patent number
US09403801B2

Reaction notes

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