Diisopropylethylamine → 1,1-Dimethylethyl 3-[5-(5-{3-cyano-4-[(2,2,2-trifluoroethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-isoquinolinyl]propanoate

HRID 2192505Notes

Reaction equation

HRID 2192505 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH2:13][C:14]([F:17])([F:16])[F:15])[C:6]([OH:8])=O)#[N:2].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:52][C:53](=[NH:73])[C:54]1[CH:63]=[CH:62][CH:61]=[C:60]2[C:55]=1[CH:56]=[CH:57][N:58]=[C:59]2[CH2:64][CH2:65][C:66]([O:68][C:69]([CH3:72])([CH3:71])[CH3:70])=[O:67]>CN(C=O)C.CO>[C:1]([C:3]1[CH:4]=[C:5]([C:6]2[O:8][N:52]=[C:53]([C:54]3[CH:63]=[CH:62][CH:61]=[C:60]4[C:55]=3[CH:56]=[CH:57][N:58]=[C:59]4[CH2:64][CH2:65][C:66]([O:68][C:69]([CH3:72])([CH3:71])[CH3:70])=[O:67])[N:73]=2)[CH:9]=[CH:10][C:11]=1[O:12][CH2:13][C:14]([F:17])([F:16])[F:15])#[N:2]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 581498983-Cyano-4-(2,2,2-trifluoroethoxy)benzoic acidHCID 178450938HCID 178450938, compound

Product 1

HCID 581498841,1-Dimethylethyl 3-[5-(5-{3-cyano-4-[(2,2,2-trifluoroethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-isoquinolinyl]propanoateYield 44.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

3-Cyano-4-[(2,2,2-trifluoroethyl)oxy]benzoic acid (D29; 0.171 g, 0.698 mmol) was stirred in DMF (4.5 ml) with HATU (0.318 g, 0.837 mmol) and DIPEA (0.366 ml, 2.093 mmol) at room temperature for 20 mins. 1,1-Dimethylethyl 3-{5-[(hydroxyamino)(imino)methyl]-1-isoquinolinyl}propanoate (D36, 0.22 g, 0.698 mmol) was added and the resulting mixture was heated to 120° C. for 30 mins in a Biotage Initiator microwave. The solvent was removed under vacuum and diethyl ether was added to the residue to give a colourless solid. Methanol was added to dissolve the brown oil remaining and the mixture filtered. A white solid was collected, which was dried in a vacuum oven to give the title compound as a white solid (164 mg).

Workup

  1. customThe solvent was removed under vacuum and diethyl ether
  2. additionwas added to the residue
  3. customto give a colourless solid
  4. dissolutionto dissolve the brown oil
  5. filtrationthe mixture filtered
  6. customA white solid was collected
  7. customwhich was dried in a vacuum oven

Sources & evidence

ORD record
ord-e7b2350120d745fc92cc9f63adc68dc2
Source dataset
uspto-grants-2012_12
Patent number
US08329730B2

Reaction notes

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