Triethylamine → 3-(5-((5-chloro-2-((2,3-dimethyl-2H-indazol-6-yl)amino)pyrimidin-4-yl)amino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-3-oxopropanenitrile

HRID 1056636Notes

Reaction equation

HRID 1056636 reaction equation
[Cl:1][C:2]1[C:3]([NH:20][CH:21]2[CH2:28][CH:24]3[CH2:25][NH:26][CH2:27][CH:23]3[CH2:22]2)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]3[C:16]([CH:17]=2)=[N:15][N:14]([CH3:18])[C:13]=3[CH3:19])=[N:6][CH:7]=1.[C:29]([CH2:31][C:32](O)=[O:33])#[N:30].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:20][CH:21]2[CH2:22][CH:23]3[CH2:27][N:26]([C:32](=[O:33])[CH2:31][C:29]#[N:30])[CH2:25][CH:24]3[CH2:28]2)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]3[C:16]([CH:17]=2)=[N:15][N:14]([CH3:18])[C:13]=3[CH3:19])=[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 1183901635-chloro-N2-(2,3-dimethyl-2H-indazol-6-yl)-N4-(octahydrocyclopenta[c]pyrrol-5-yl)pyrimidine-2,4-diamine

Product 1

HCID 1183901803-(5-((5-chloro-2-((2,3-dimethyl-2H-indazol-6-yl)amino)pyrimidin-4-yl)amino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-3-oxopropanenitrileYield 87%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-chloro-N2-(2,3-dimethyl-2H-indazol-6-yl)-N4-(octahydrocyclopenta[c]pyrrol-5-yl)pyrimidine-2,4-diamine (484.7 mg, 1.22 mmol) and 2-cyanoacetic acid (155.0 mg, 1.82 mmol) in a mixture of DCM (40 mL) and DMF (10 mL) were added HATU (673.2 mg, 1.77 mmol) and Et3N (0.60 g, 5.90 mmol). The reaction mixture was stirred at rt for 5.5 h, 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 (DCM/MeOH (v/v)=40/1) to give the title compound as a beige solid (0.49 g, 87%).

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 (DCM/MeOH (v/v)=40/1)

Sources & evidence

ORD record
ord-42a063416e8847689b02b069acc922ad
Source dataset
uspto-grants-2016_07
Patent number
US09399637B2

Reaction notes

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