Triethylamine → 3-(8-((2-((2,3-dimethyl-2H-indazol-6-yl)amino)pyrimidin-4-yl)(methyl)amino)-2-azaspiro[4.5]decan-2-yl)-3-oxopropanenitrile

HRID 1056628Notes

Reaction equation

HRID 1056628 reaction equation
[CH3:1][N:2]1[C:10]([CH3:11])=[C:9]2[C:4]([CH:5]=[C:6]([NH:12][C:13]3[N:18]=[C:17]([N:19]([CH3:30])[CH:20]4[CH2:29][CH2:28][C:23]5([CH2:27][NH:26][CH2:25][CH2:24]5)[CH2:22][CH2:21]4)[CH:16]=[CH:15][N:14]=3)[CH:7]=[CH:8]2)=[N:3]1.[C:31]([CH2:33][C:34](O)=[O:35])#[N:32].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>[CH3:1][N:2]1[C:10]([CH3:11])=[C:9]2[C:4]([CH:5]=[C:6]([NH:12][C:13]3[N:18]=[C:17]([N:19]([CH3:30])[CH:20]4[CH2:29][CH2:28][C:23]5([CH2:27][N:26]([C:34](=[O:35])[CH2:33][C:31]#[N:32])[CH2:25][CH2:24]5)[CH2:22][CH2:21]4)[CH:16]=[CH:15][N:14]=3)[CH:7]=[CH:8]2)=[N:3]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 118406568N2-(2,3-dimethyl-2H-indazol-6-yl)-N4-methyl-N4-(2-azaspiro[4.5]decan-8-yl)pyrimidine-2,4-diamine

Product 1

HCID 1183901603-(8-((2-((2,3-dimethyl-2H-indazol-6-yl)amino)pyrimidin-4-yl)(methyl)amino)-2-azaspiro[4.5]decan-2-yl)-3-oxopropanenitrileYield 60%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of N2-(2,3-dimethyl-2H-indazol-6-yl)-N4-methyl-N4-(2-azaspiro[4.5]decan-8-yl)pyrimidine-2,4-diamine (300 mg, 0.74 mmol), 2-cyanoacetic acid (156 mg, 1.83 mmol) in a mixture of DCM and DMF (4/1 (v/v), 35 mL) were added HATU (925.8 mg, 2.44 mmol) and Et3N (0.49 g, 4.84 mmol). After addition, the reaction mixture was stirred at rt for 0.5 h, then quenched with H2O (30 mL) and extracted with DCM (100 mL×3). The combined organic phases were washed with brine (100 mL), and dried over anhydrous Na2SO4, then concentrated in vacuo. The residue was purified by silica gel column chromatography (DCM/MeOH (v/v)=20/1) to give the title compound as a beige solid (210 mg, 60.0%).

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. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography (DCM/MeOH (v/v)=20/1)

Sources & evidence

ORD record
ord-59adcb1d1ade49e192ebd4529eceee35
Source dataset
uspto-grants-2016_07
Patent number
US09399637B2

Reaction notes

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