Diisopropylethylamine → HCID 86732137, compound

HRID 930307Notes

Reaction equation

HRID 930307 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C@:8]2([CH3:26])[CH2:13][C@@H:12]([C:14]([F:17])([F:16])[F:15])[O:11][C:10]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[N:9]2)[C:5]([F:27])=[CH:4][CH:3]=1.[C:28]([C:30]1[CH:31]=[CH:32][C:33]([C:36](O)=[O:37])=[N:34][CH:35]=1)#[N:29].C(N(C(C)C)CC)(C)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>CCOC(C)=O.C(=O)(O)[O-].[Na+]>[C:28]([C:30]1[CH:31]=[CH:32][C:33]([C:36]([NH:1][C:2]2[N:7]=[C:6]([C@:8]3([CH3:26])[CH2:13][C@@H:12]([C:14]([F:17])([F:15])[F:16])[O:11][C:10]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[N:9]3)[C:5]([F:27])=[CH:4][CH:3]=2)=[O:37])=[N:34][CH:35]=1)#[N:29]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 124007345-Cyanopyridine-2-carboxylic acidHCID 86732135HCID 86732135, compound

Product 1

HCID 86732137HCID 86732137, compoundYield 146.2%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of tert-butyl ((4S,6S)-4-(6-amino-3-fluoropyridin-2-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)carbamate (7k, 0.101 mg, 0.13 mmol) in EtOAc (4 mL) was added 5-cyano-2-pyridinecarboxylic acid (0.042 mg, 0.28 mmol, Aldrich), di-isopropylethylamine (0.09 mL, 0.51 mmol), and 1-propanephosphonic acid cyclic anhydride (0.18 mL, 0.28 mmol, 50 wt. % solution in ethyl acetate, Alfa-Aesar). The reaction mixture was stirred at room temperature for 2 hs. The reaction was diluted with saturated aqueous sodium bicarbonate and extracted with EtOAc (10 mL). The organic layer was washed sequentially with water and brine and dried over sodium sulfate. The solution was concentrated under reduced pressure and the crude material was purified via silica gel flash chromatography (gradient 0-30% EtOAc in hexanes) to afford the title compound as a white solid (0.097 g, 0.19 mmol, 72% yield). MS m/z=523.2 [M+H]+. Calculated for C23H22F4N6O4: 522.4

Workup

  1. extractionextracted with EtOAc (10 mL)
  2. washThe organic layer was washed sequentially with water and brine
  3. dry with materialdried over sodium sulfate
  4. concentrationThe solution was concentrated under reduced pressure
  5. customthe crude material was purified via silica gel flash chromatography (gradient 0-30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-d0376399ab7d40ea96516eb81efcb817
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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