4-Methylmorpholine → HCID 178481055, compound

HRID 467675Notes

Reaction equation

HRID 467675 reaction equation
[CH:1]1([C:4]2[N:9]=[C:8]([C:10]([NH:12][C:13]3[C:14]([C:19](O)=[O:20])=[N:15][N:16]([CH3:18])[CH:17]=3)=[O:11])[C:7]([NH:22][C:23]3[CH:24]=[N:25][CH:26]=[N:27][CH:28]=3)=[CH:6][CH:5]=2)[CH2:3][CH2:2]1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:60][C:61]1([CH3:66])[CH2:65][CH2:64][CH2:63][NH:62]1>CN(C=O)C>[CH:1]1([C:4]2[N:9]=[C:8]([C:10](=[N:12][C:13]3[C:14]([C:19]([N:62]4[CH2:63][CH2:64][CH2:65][C:61]4([CH3:66])[CH3:60])=[O:20])=[N:15][N:16]([CH3:18])[CH:17]=3)[OH:11])[C:7]([NH:22][C:23]3[CH:28]=[N:27][CH:26]=[N:25][CH:24]=3)=[CH:6][CH:5]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 4147732,2-DimethylpyrrolidineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 701164844-{[6-Cyclopropyl-3-(pyrimidin-5-ylamino)-pyridine-2-carbonyl]-amino}-1-methyl-1H-pyrazole-3-carboxylic acid

Product 1

HCID 178481055HCID 178481055, compoundYield 7.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To stirred solution of 4-{[6-cyclopropyl-3-(pyrimidin-5-ylamino)-pyridine-2-carbonyl]-amino}-1-methyl-1H-pyrazole-3-carboxylic acid (70 mg, 0.18 mmol) in DMF were sequentially added N-methylmorpholine (0.12 ml, 0.9 mmol), HBTU (210 mg, 0.55 mmol), and 2,2-dimethylpyrrolidine (35 mg, 0.36 mmol) at rt, and the reaction mixture was allowed to stirr overnight. The solvent was removed in vacuo, and the residue was dissolved in EtOAc (10 ml), and was washed with aqueous NaHCO3 solution and water. The aqueous layer was back-extracted with EtOAc, and the combined organic layer was dried (Na2SO4), filtered, and evaporated in vacuo. The crude product was purified by prep. HPLC (column: Gemini C18 (250×21.2 mm, 5μ); elution with a gradient of 0.05% aqueous TFA solution/acetonitrile) to give the title compound (6 mg, 6%) as sticky yellow solid.

Workup

  1. customat rt
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue was dissolved in EtOAc (10 ml)
  4. washwas washed with aqueous NaHCO3 solution and water
  5. extractionThe aqueous layer was back-extracted with EtOAc
  6. dry with materialthe combined organic layer was dried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe crude product was purified by prep
  10. washelution with a gradient of 0.05% aqueous TFA solution/acetonitrile)

Sources & evidence

ORD record
ord-3c976982d1f94f6f97fdadaafff57e62
Source dataset
uspto-grants-2014_01
Patent number
US08623866B2

Reaction notes

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