4-Methylmorpholine → HCID 117864700, compound

HRID 1486337Notes

Reaction equation

HRID 1486337 reaction equation
Br.Br.[CH3:3][C:4]1([NH2:9])[CH2:6][C:5]1([CH3:8])[NH2:7].[F:10][C:11]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[C:12]=1[CH2:13][O:14][C:15]1[N:20]2[N:21]=[C:22]([CH3:27])[C:23]([C:24](O)=[O:25])=[C:19]2[CH:18]=[C:17]([CH3:28])[CH:16]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>CN(C=O)C.ClCCl>[NH2:7][C:5]1([CH3:8])[CH2:6][C:4]1([NH:9][C:24]([C:23]1[C:22]([CH3:27])=[N:21][N:20]2[C:15]([O:14][CH2:13][C:12]3[C:29]([F:33])=[CH:30][CH:31]=[CH:32][C:11]=3[F:10])=[CH:16][C:17]([CH3:28])=[CH:18][C:19]=12)=[O:25])[CH3:3]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 90120336HCID 90120336, compoundHCID 117859510HCID 117859510, compound

Product 1

HCID 117864700HCID 117864700, compound

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent2×

Procedure

29 mg (0.11 mmol) of rac-1,2-dimethylcyclopropane-1,2-diamine dihydrobromide (described in: W. v. d. Saal et al. Liebigs Annalen der Chemie 1994, 569-580) were initially charged in a 96-well deep-well multititre plate. A solution of 33.2 mg (0.1 mmol) of 7-[(2,6-difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic acid from Example 4A in 0.4 ml of DMF/dichloromethane (1:1, v/v) and a solution of 49.4 mg (0.13 mmol) of HATU in 0.4 ml of DMF/dichloromethane (1:1, v/v) were added successively. After adding 20.2 mg (0.20 mmol) of 4-methylmorpholine, the mixture was shaken at RT overnight. Subsequently, the mixture was heated to 60° C. and shaken at this temperature for 7 h. Then the solvent was evaporated off completely. The residue was dissolved in 0.8 ml of DMF and filtered, and the target compound was isolated 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. 2.3 mg (5% of theory) of the title compound were obtained.

Workup

  1. temperatureSubsequently, the mixture was heated to 60° C.
  2. stirringshaken at this temperature for 7 h
  3. customThen the solvent was evaporated off completely
  4. dissolutionThe residue was dissolved in 0.8 ml of DMF
  5. filtrationfiltered
  6. customthe target compound was isolated by preparative LC-MS (Method 9)
  7. concentrationThe product-containing fractions were concentrated under reduced pressure
  8. dissolutionThe residue of each product fraction was dissolved in 0.6 ml of DMSO

Sources & evidence

ORD record
ord-f8ad7ad732084047a9bd51f818aade01
Source dataset
uspto-grants-2016_08
Patent number
US09422285B2

Reaction notes

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