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

HRID 1478044Notes

Reaction equation

HRID 1478044 reaction equation
[Cl:1][C:2]1[C:3]([NH:16][CH:17]2[CH2:24][CH:20]3[CH2:21][NH:22][CH2:23][CH:19]3[CH2:18]2)=[N:4][C:5]([NH:8][C:9]2[CH:13]=[C:12]([CH3:14])[N:11]([CH3:15])[N:10]=2)=[N:6][CH:7]=1.[C:25]([CH2:27][C:28](O)=[O:29])#[N:26].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:16][CH:17]2[CH2:24][CH:20]3[CH2:21][N:22]([C:28](=[O:29])[CH2:27][C:25]#[N:26])[CH2:23][CH:19]3[CH2:18]2)=[N:4][C:5]([NH:8][C:9]2[CH:13]=[C:12]([CH3:14])[N:11]([CH3:15])[N:10]=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 1183900025-chloro-N2-(1,5-dimethyl-1H-pyrazol-3-yl)-N4-(octahydro cyclopenta[c]pyrrol-5-yl)pyrimidine-2,4-diamine

Product 1

HCID 1183900783-(5-((5-chloro-2-((1,5-dimethyl-1H-pyrazol-3-yl)amino)pyrimidin-4-yl)amino)hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-3-oxopropanenitrileYield 73.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-chloro-N2-(1,5-dimethyl-1H-pyrazol-3-yl)-N4-(octahydro cyclopenta[c]pyrrol-5-yl)pyrimidine-2,4-diamine (522.0 mg, 1.50 mmol) and 2-cyanoacetic acid (127.6 mg, 1.50 mmol) in a mixture of DCM (40 mL) and DMF (10 mL) were added HATU (690.2 mg, 1.82 mmol) and Et3N (313.5 mg, 3.10 mmol). After addition, the reaction mixture was stirred at rt for 1.5 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)=80/1) to give the title compound as a beige solid (455.2 mg, 73.1%).

Workup

  1. additionAfter addition
  2. customquenched with H2O (30 mL)
  3. extractionextracted with DCM (100 mL×3)
  4. washThe combined organic phases were washed with brine (100 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)=80/1)

Sources & evidence

ORD record
ord-21cfe918d50c4e66a9fb042b7051bc16
Source dataset
uspto-grants-2016_08
Patent number
US09403801B2

Reaction notes

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