2-Methylpropylenediamine → N-(2-Amino-2-methylpropyl)-7-[(2,6-difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxamide formate

HRID 1486331Notes

Reaction equation

HRID 1486331 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:16])=[C:10]2[CH:9]=[C:8]([CH3:19])[CH:7]=1.[NH2:25][CH2:26][C:27]([NH2:30])([CH3:29])[CH3:28].C(N(CC)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.O>[CH:15]([OH:17])=[O:16].[NH2:30][C:27]([CH3:29])([CH3:28])[CH2:26][NH:25][C:15]([C:14]1[C:13]([CH3:18])=[N:12][N:11]2[C:6]([O:5][CH2:4][C:3]3[C:2]([F:1])=[CH:23][CH:22]=[CH:21][C:20]=3[F:24])=[CH:7][C:8]([CH3:19])=[CH:9][C:10]=12)=[O:17]

Participants

7

Reactant 4

HCID 131282-MethylpropylenediamineHCID 81531DiisopropylethylamineHCID 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 121434559N-(2-Amino-2-methylpropyl)-7-[(2,6-difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxamide formateYield 42.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 78.0 mg (0.235 mmol, 1.0 eq.) of 7-[(2,6-difluorobenzyl)oxy]-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic acid from Example 4A, 49 μl (0.47 mmol, 2.0 eq.) of 1,2-diamino-2-methylpropane [CAS No.: 811-93-8] and 0.20 ml (1.2 mmol, 5.0 eq.) of N,N-diisopropylethylamine in 2.4 ml of DMF was admixed with 116 mg of HATU (0.305 mmol, 1.3 eq.) and stirred at RT for 6 h. Subsequently, water was added and the mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulphate, filtered and concentrated. The residue was stirred with water, and the precipitated solids were filtered off and purified by means of preparative HPLC (Method 4). 22.3 mg of the title compound were obtained (24% of theory).

Workup

  1. extractionthe mixture was extracted three times with ethyl acetate
  2. washThe combined organic phases were washed with saturated aqueous sodium chloride solution
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. stirringThe residue was stirred with water
  7. filtrationthe precipitated solids were filtered off
  8. custompurified by means of preparative HPLC (Method 4)

Sources & evidence

ORD record
ord-ca8a91d3665a430087a660ecc67a4fea
Source dataset
uspto-grants-2016_08
Patent number
US09422285B2

Reaction notes

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