Diisopropylethylamine → HCID 44476578, compound

HRID 2192528Notes

Reaction equation

HRID 2192528 reaction equation
[F:1][CH:2]([F:13])[O:3][C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=1.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:48][C:49]([C:51]1[C:52]2[CH:53]=[CH:54][N:55]=[CH:56][C:57]=2[CH:58]=[CH:59][CH:60]=1)=[NH:50]>CN(C=O)C>[F:13][CH:2]([F:1])[O:3][C:4]1[CH:5]=[CH:6][C:7]([C:8]2[O:10][N:50]=[C:49]([C:51]3[CH:60]=[CH:59][CH:58]=[C:57]4[C:52]=3[CH:53]=[CH:54][N:55]=[CH:56]4)[N:48]=2)=[CH:11][CH:12]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 7373604-(Difluoromethoxy)benzoic 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 44476578HCID 44476578, compoundYield 26.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
110 °C

Procedure

4-[(Difluoromethyl)oxy]benzoic acid (Aldrich; 121 mg, 0.642 mmol) was stirred in DMF (1 ml) with HATU (244 mg, 0.642 mmol) and DIPEA (0.28 ml, 1.605 mmol) at room temperature for 30 mins before adding a solution of N-hydroxy-5-isoquinolinecarboximidamide (D1, 100 mg, 0.535 mmol) in DMF (1 ml). The resulting mixture was heated to 110° C. for 2 hrs in a Biotage Initiator microwave. The solvent was removed under vacuum and the residue was purified by column chromatography on silica, eluting with 0-100% ethyl acetate in cyclohexane. The relevant fractions were combined and concentrated under vacuum to provide a crude material, which was further purified by Mass Directed Preparative HPLC (Supelcosil ABZ+Plus column, eluting with solvents A/B (A: Water+0.1% Formic acid, B: MeCN:Water 95:5+0.05% Formic acid)) to give the title compound as a white solid (48 mg).

Workup

  1. customThe solvent was removed under vacuum
  2. customthe residue was purified by column chromatography on silica
  3. washeluting with 0-100% ethyl acetate in cyclohexane
  4. concentrationconcentrated under vacuum
  5. customto provide a crude material, which
  6. customwas further purified by Mass Directed Preparative HPLC (Supelcosil ABZ+Plus column
  7. washeluting with solvents A/B (A: Water+0.1% Formic acid, B

Sources & evidence

ORD record
ord-860f589dda02447c9b0d39103317f2d0
Source dataset
uspto-grants-2012_12
Patent number
US08329730B2

Reaction notes

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