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

HRID 1478041Notes

Reaction equation

HRID 1478041 reaction equation
[Cl:1][C:2]1[C:3]([NH:16][CH:17]2[CH2:27][CH2:26][C:20]3([CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)[CH2:19][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:28]([CH2:30][C:31](O)=[O:32])#[N:29].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl.CN(C)C=O>[Cl:1][C:2]1[C:3]([NH:16][CH:17]2[CH2:18][CH2:19][C:20]3([CH2:25][CH2:24][N:23]([C:31](=[O:32])[CH2:30][C:28]#[N:29])[CH2:22][CH2:21]3)[CH2:26][CH2:27]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 1183900765-chloro-N2-(1,5-dimethyl-1H-pyrazol-3-yl)-N4-(3-azaspiro[5.5]undecan-9-yl)pyrimidine-2,4-diamine

Product 1

HCID 1183901123-(9-((5-chloro-2-((1,5-dimethyl-1H-pyrazol-3-yl)amino)pyrimidin-4-yl)amino)-3-azaspiro[5.5]undecan-3-yl)-3-oxopropanenitrileYield 54.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-chloro-N2-(1,5-dimethyl-1H-pyrazol-3-yl)-N4-(3-azaspiro[5.5]undecan-9-yl)pyrimidine-2,4-diamine (200.5 mg, 0.5142 mmol) in dichloromethane (28 mL) and N,N-dimethylformamide (7 mL) were added 2-cyanoacetic acid (110.3 mg, 1.297 mmol), N,N-diethylethanamine (156.5 mg, 1.547 mmol) and HATU (585.4 mg, 1.540 mmol). The mixture was stirred at room temperature for 4 h and concentrated in vacuo. The residue was purified by flash silica gel column chromatography (DCM/MeOH (v/v)=50/1 to 10/1) to give the title compound as a white solid (128.5 mg, 54.68%).

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was purified by flash silica gel column chromatography (DCM/MeOH (v/v)=50/1 to 10/1)

Sources & evidence

ORD record
ord-5d634bd8640b4284908dbb928bd12948
Source dataset
uspto-grants-2016_08
Patent number
US09403801B2

Reaction notes

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