4-Methylmorpholine → 7-[(2,6-Difluorobenzyl)oxy]-2,5-dimethyl-N-(morpholin-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

HRID 1486340Notes

Reaction equation

HRID 1486340 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:3]=1[CH2:4][O:5][C:6]1[N:11]2[N:12]=[C:13]([CH3:18])[C:14]([C:15]([OH:17])=O)=[C:10]2[CH:9]=[C:8]([CH3:19])[CH:7]=1.[N:25]1([NH2:31])[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>CN(C=O)C>[F:1][C:2]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:3]=1[CH2:4][O:5][C:6]1[N:11]2[N:12]=[C:13]([CH3:18])[C:14]([C:15]([NH:31][N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[O:17])=[C:10]2[CH:9]=[C:8]([CH3:19])[CH:7]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 20315N-AminomorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 117859510HCID 117859510, compound

Product 1

HCID 1178596787-[(2,6-Difluorobenzyl)oxy]-2,5-dimethyl-N-(morpholin-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

33 mg (0.10 mmol) of 7-[(2,6-difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic acid from Example 4A were initially charged in a 96-well deep well multititre plate. A solution of 17 mg (0.10 mmol) of morpholine-4-amine in 0.4 ml of DMF and a solution of 45.6 mg (0.12 mol) of HATU in 0.4 ml of DMF were added successively. After adding 20.2 mg (0.20 mmol) of 4-methylmorpholine, the mixture was shaken at RT overnight. Then the mixture was filtered and the target compound was isolated from the filtrate by preparative LC-MS (Method 9). The product-containing fractions were concentrated under reduced pressure using a centrifugal dryer. The residue of each product fraction was dissolved in 0.6 ml of DMSO. These were combined and finally freed of the solvent in a centrifugal dryer. 0.5 mg (1% of theory) were obtained.

Workup

  1. filtrationThen the mixture was filtered
  2. customthe target compound was isolated from the filtrate by preparative LC-MS (Method 9)
  3. concentrationThe product-containing fractions were concentrated under reduced pressure
  4. dissolutionThe residue of each product fraction was dissolved in 0.6 ml of DMSO
  5. custom0.5 mg (1% of theory) were obtained

Sources & evidence

ORD record
ord-4b32cba6c7ca4010bc997f38bc03a3ce
Source dataset
uspto-grants-2016_08
Patent number
US09422285B2

Reaction notes

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