Diisopropylethylamine → N-(5-(2-(2,2-dimethylpyrrolidin-1-yl)ethylcarbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo(1,5-a)pyridine-3-carboxamide

HRID 1521336Notes

Reaction equation

HRID 1521336 reaction equation
[CH3:1][C:2]1[C:10]([NH:11][C:12]([C:14]2[CH:15]=[N:16][N:17]3[CH:22]=[C:21]([C:23]4[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=4)[CH:20]=[CH:19][C:18]=23)=[O:13])=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=1.[CH3:29][C:30]1([CH3:38])[CH2:34][CH2:33][CH2:32][N:31]1[CH2:35][CH2:36][NH2:37].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:29][C:30]1([CH3:38])[CH2:34][CH2:33][CH2:32][N:31]1[CH2:35][CH2:36][NH:37][C:6]([C:5]1[CH:9]=[C:10]([NH:11][C:12]([C:14]2[CH:15]=[N:16][N:17]3[CH:22]=[C:21]([C:23]4[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=4)[CH:20]=[CH:19][C:18]=23)=[O:13])[C:2]([CH3:1])=[N:3][CH:4]=1)=[O:8]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 451570772-(2,2-Dimethylpyrrolidin-1-yl)ethan-1-amineHCID 712833496-Methyl-5-(6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)nicotinic Acid

Product 1

HCID 71283628N-(5-(2-(2,2-dimethylpyrrolidin-1-yl)ethylcarbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo(1,5-a)pyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-Methyl-5-(6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)nicotinic acid (6.6 g, 1.1 equiv) and 2-(2,2-dimethylpyrrolidin-1-yl)ethanamine (2.397 g, 11.14 mmol) were combined in DMF (100 ml) and treated with DIPEA (8.34 ml, 47.7 mmol) followed by HATU (4.44 g, 11.67 mmol). After stiring at RT for 90 mins, the mixture was partitioned between water (1 L) and EtOAc (750 ml). The resulting suspension was removed by filtration and the organic portion was washed with aqueous sodium bicarbonate, 0.5M lithium chloride, brine, dried MgSO4, filtered and evaporated to dryness. Purification by chromatography on silica eluting with 0-20% 2M NH3 in MeOH/TBME afforded residue which was recrystallised from acetone to afford the title compound;

Workup

  1. customthe mixture was partitioned between water (1 L) and EtOAc (750 ml)
  2. customThe resulting suspension was removed by filtration
  3. washthe organic portion was washed with aqueous sodium bicarbonate, 0.5M lithium chloride, brine, dried MgSO4
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customPurification by chromatography on silica eluting with 0-20% 2M NH3 in MeOH/TBME afforded residue which
  7. customwas recrystallised from acetone

Sources & evidence

ORD record
ord-890a7c7bf42646bb85cfac076c992856
Source dataset
uspto-grants-2015_07
Patent number
US09073921B2

Reaction notes

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