Cyanoacetic acid → 3-(9-((5-chloro-2-((1-(2-hydroxyethyl)-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)amino)-3-azaspiro[5.5]undecan-3-yl)-3-oxopropanenitrile

HRID 1478060Notes

Reaction equation

HRID 1478060 reaction equation
[CH2:1]1[C:6]2([CH2:11][CH2:10][CH:9]([NH:12][C:13]3[C:18]([Cl:19])=[CH:17][N:16]=[C:15]([NH:20][C:21]4[CH:22]=[N:23][N:24]([CH2:26][CH2:27][OH:28])[CH:25]=4)[N:14]=3)[CH2:8][CH2:7]2)[CH2:5][CH2:4][NH:3][CH2:2]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>ClCCl.CN(C=O)C.O>[Cl:19][C:18]1[C:13]([NH:12][CH:9]2[CH2:10][CH2:11][C:6]3([CH2:5][CH2:4][N:3]([C:32](=[O:33])[CH2:31][C:29]#[N:30])[CH2:2][CH2:1]3)[CH2:7][CH2:8]2)=[N:14][C:15]([NH:20][C:21]2[CH:22]=[N:23][N:24]([CH2:26][CH2:27][OH:28])[CH:25]=2)=[N:16][CH:17]=1

Participants

7

Reactant 3

HCID 9740Cyanoacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 1183900472-(4-((4-(3-azaspiro[5.5]undecan-9-ylamino)-5-chloropyrimidin-2-yl)amino)-1H-pyrazol-1-yl)ethanol

Product 1

HCID 1183900383-(9-((5-chloro-2-((1-(2-hydroxyethyl)-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)amino)-3-azaspiro[5.5]undecan-3-yl)-3-oxopropanenitrileYield 44.94%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-[4-[[4-(3-azaspiro[5.5]undecan-9-ylamino)-5-chloropyrimidin-2-yl]amino]-1H-pyrazol-1-yl]ethanol (200.5 mg, 0.4940 mmol) in a mixture of dichloromethane (40 mL) and DMF (10 mL) were added 2-cyanoacetic acid (46.5 mg, 0.547 mmol), HATU (375.2 mg, 0.9868 mmol) and TEA (100.5 mg, 0.9932 mmol). The mixture was stirred at room temperature for 2 h. The mixture was diluted with water (50 mL), and extracted with DCM/MeOH (10/1, 50 mL×3). The combined organic layer was 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 10/1) to give the product as a yellow solid (105 mg, 44.94%).

Workup

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

Sources & evidence

ORD record
ord-a4a80523a7454d47bb84a054f6410893
Source dataset
uspto-grants-2016_08
Patent number
US09403801B2

Reaction notes

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