Triethylamine → 3-(9-((5-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)amino)-3-azaspiro[5.5]undecan-3-yl)-3-oxopropanenitrile

HRID 1478030Notes

Reaction equation

HRID 1478030 reaction equation
[CH3:1][C:2]1[C:3]([NH:15][CH:16]2[CH2:26][CH2:25][C:19]3([CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)[CH2:18][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:27]([CH2:29][C:30](O)=[O:31])#[N:28].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][C:2]1[C:3]([NH:15][CH:16]2[CH2:26][CH2:25][C:19]3([CH2:24][CH2:23][N:22]([C:30](=[O:31])[CH2:29][C:27]#[N:28])[CH2:21][CH2:20]3)[CH2:18][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 1183900055-methyl-N2-(1-methyl-1H-pyrazol-4-yl)-N4-(3-azaspiro[5.5]undecan-9-yl)pyrimidine-2,4-diamine

Product 1

HCID 1183899923-(9-((5-methyl-2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)amino)-3-azaspiro[5.5]undecan-3-yl)-3-oxopropanenitrileYield 56.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-methyl-N2-(1-methyl-1H-pyrazol-4-yl)-N4-(3-azaspiro[5.5]undecan-9-yl)pyrimidine-2,4-diamine (100 mg, 0.28 mmol), 2-cyanoacetic acid (43.3 mg, 0.51 mmol) in a mixture of DCM and DMF (20 mL/5 mL) were added HATU (241.9 mg, 0.64 mmol) and Et3N (85.8 mg, 0.85 mmol). After addition, 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, then filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (DCM/MeOH (v/v)=10/1) to give the title compound as a beige solid (66.8 mg, 56%).

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)=10/1)

Sources & evidence

ORD record
ord-334b3459c81847a9b6ed0822f0e19429
Source dataset
uspto-grants-2016_08
Patent number
US09403801B2

Reaction notes

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