Diisopropylethylamine → 5-{5-[4-[(1-Methylethyl)oxy]-3-(methyloxy)phenyl]-1,2,4-oxadiazol-3-yl}isoquinoline

HRID 2192521Notes

Reaction equation

HRID 2192521 reaction equation
[CH3:1][CH:2]([O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][C:6]=1[O:14][CH3:15])[CH3:3].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.O[NH:50][C:51]([C:53]1[C:54]2[CH:55]=[CH:56][N:57]=[CH:58][C:59]=2[CH:60]=[CH:61][CH:62]=1)=[NH:52]>CN(C)C=O>[CH3:3][CH:2]([O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]2[O:11][N:52]=[C:51]([C:53]3[CH:62]=[CH:61][CH:60]=[C:59]4[C:54]=3[CH:55]=[CH:56][N:57]=[CH:58]4)[N:50]=2)=[CH:7][C:6]=1[O:14][CH3:15])[CH3:1]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 20639154-Isopropoxy-3-methoxybenzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178513273HCID 178513273, compound

Product 1

HCID 444764895-{5-[4-[(1-Methylethyl)oxy]-3-(methyloxy)phenyl]-1,2,4-oxadiazol-3-yl}isoquinoline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of 4-[(1-methylethyl)oxy]-3-(methyloxy)benzoic acid (Journal of the American Chemical Society (1955), 77 757-8; 135 mg, 0.641 mmol), HATU (244 mg, 0.641 mmol), Hunig's base (0.3 ml, 1.718 mmol) in N,N-dimethylformamide (DMF) (1 ml) was stirred at room temperature for 1 hr before the addition of N-hydroxy-5-isoquinolinecarboximidamide (D1; 100 mg, 0.534 mmol) in N,N-dimethylformamide (DMF) (1 ml). The reaction mixture was stirred at room temperature for 2-3 hrs and then heated in a microwave at 140° C. for 1.5 hr. The reaction mixture was concentrated in vacuo, dissolved in 1-2 ml of N-methylpyrrolidinone and purified by Preparative HPLC (Waters Sunfire C18 column, eluting with solvents A/B (A: Water+0.1% Formic acid, B: MeCN+0.1% Formic acid)). The solvent was evaporated in vacuo to give the title compound (5 mg).

Workup

  1. temperatureheated in a microwave at 140° C. for 1.5 hr
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutiondissolved in 1-2 ml of N-methylpyrrolidinone
  4. custompurified by Preparative HPLC (Waters Sunfire C18 column
  5. washeluting with solvents A/B (A: Water+0.1% Formic acid, B
  6. customThe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-192a644dc77c4e949ac4c6912df1b6de
Source dataset
uspto-grants-2012_12
Patent number
US08329730B2

Reaction notes

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