Diisopropylethylamine → HCID 86679234, compound

HRID 1774884Notes

Reaction equation

HRID 1774884 reaction equation
Cl.[CH3:2][N:3]1[C:12]2[C:7](=[CH:8][C:9]([C:13]3[CH:14]=[N:15][CH:16]=[C:17]([O:19][C@H:20]4[CH2:24][CH2:23][NH:22][CH2:21]4)[CH:18]=3)=[CH:10][CH:11]=2)[CH2:6][CH2:5][C:4]1=[O:25].[CH3:26][N:27]1[CH:31]=[C:30]([C:32](O)=[O:33])[CH:29]=[N:28]1.CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>CCOC(C)=O>[CH3:2][N:3]1[C:12]2[C:7](=[CH:8][C:9]([C:13]3[CH:14]=[N:15][CH:16]=[C:17]([O:19][C@H:20]4[CH2:24][CH2:23][N:22]([C:32]([C:30]5[CH:29]=[N:28][N:27]([CH3:26])[CH:31]=5)=[O:33])[CH2:21]4)[CH:18]=3)=[CH:10][CH:11]=2)[CH2:6][CH2:5][C:4]1=[O:25]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 6431601-Methyl-1H-pyrazole-4-carboxylic acidHCID 86679170HCID 86679170, compound

Product 1

HCID 86679234HCID 86679234, compoundYield 75.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent3×

Procedure

To a solution of 1-methyl-6-[5-((S)-pyrrolidin-3-yloxy)-pyridin-3-yl]-3,4-dihydro-1H-quinolin-2-one hydrochloride (0.04 g, 0.111 mmol, example 60), 1-methyl-1H-pyrazole-4-carboxylic acid (0.021 g, 0.167 mmol) and Hunig's base (0.036 g, 0.278 mmol) in EtOAc (2 mL) was added propylphosphonic acid anhydride (cyclic trimer) solution (50% in EtOAc, 0.177 mL, 0.25 mmol) dropwise and the reaction mixture was stirred at room temperature over night. The mixture was diluted with EtOAc, poured into a sat. NaHCO3 solution (5 mL) and extracted with EtOAc (2×20 mL). Combined organics were dried over Na2SO4, filtered and evaporated. The residue was purified by silica gel flash chromatography eluting with a 0 to 10% MeOH-DCM gradient to give the title compound (0.036 g, 75.1%) as a colorless amorphous solid. MS: 432.4 (M+H+).

Workup

  1. extractionextracted with EtOAc (2×20 mL)
  2. dry with materialCombined organics were dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was purified by silica gel flash chromatography
  6. washeluting with a 0 to 10% MeOH-DCM gradient

Sources & evidence

ORD record
ord-b04e9b1dbc3946fa9e8e0ace8d577f56
Source dataset
uspto-grants-2016_02
Patent number
US09260408B2

Reaction notes

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