Diisopropylethylamine → HCID 24985808, compound

HRID 2101846Notes

Reaction equation

HRID 2101846 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[Cl:44][C:45]1[C:53]([C:54]#[N:55])=[CH:52][CH:51]=[C:50]2[C:46]=1[CH:47]=[C:48]([CH:62]([F:64])[F:63])[N:49]2[CH2:56]/[C:57](=[N:60]/[H])/[NH:58]O>CN(C=O)C.C1COCC1.O>[Br:1][C:2]1[CH:10]=[C:6]([C:7]2[O:9][N:60]=[C:57]([CH2:56][N:49]3[C:50]4[C:46](=[C:45]([Cl:44])[C:53]([C:54]#[N:55])=[CH:52][CH:51]=4)[CH:47]=[C:48]3[CH:62]([F:64])[F:63])[N:58]=2)[CH:5]=[N:4][CH:3]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 887075-Bromonicotinic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178506479HCID 178506479, compound

Product 1

HCID 24985808HCID 24985808, compoundYield 31%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-bromonicotinic acid (0.017 g, 0.082 mmol) in anhydrous DMF (2 mL) was added HATU (0.031 g, 0.082 mmol) and DIEA (0.011 g, 0.082 mmol) and stirred at rt. After 10 min, a solution of (1Z)-2-[4-chloro-5-cyano-2-(difluoromethyl)-1H-indol-1-yl]-N-hydroxyethanimidamide (0.023 g, 0.077 mmol) in THF (1.5 mL) was added and stirring was continued at rt. After 30 min, the mixture was heated in a microwave at 150° C. for 20 min. Upon cooling, water (˜5 mL) was added to the stirring reaction mixture and the precipitated solids were collected by filtration and washed sequentially with water and hexanes. The product was further purified by flash chromatography (0-20% EtOAc-hexanes gradient), followed by crystallization from CH2Cl2-hexanes to afford the title compound as a white solid (0.011 g, 31% yield): MS (ES) m/z 464 and 466 (M+1 Br isotopes).

Workup

  1. stirringstirring
  2. customwas continued at rt
  3. waitAfter 30 min
  4. temperaturethe mixture was heated in a microwave at 150° C. for 20 min
  5. temperatureUpon cooling
  6. filtrationthe precipitated solids were collected by filtration
  7. washwashed sequentially with water and hexanes
  8. customThe product was further purified by flash chromatography (0-20% EtOAc-hexanes gradient)
  9. customfollowed by crystallization from CH2Cl2-hexanes

Sources & evidence

ORD record
ord-55cf9a5d588f452a87b9aaf0dac71c76
Source dataset
uspto-grants-2009_08
Patent number
US07572820B2

Reaction notes

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