1-Hydroxybenzotriazole → HCID 86653626, compound

HRID 453398Notes

Reaction equation

HRID 453398 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[CH:18]=[C:17]2[C:13]([CH2:14][NH:15][C:16]2=[O:19])=[CH:12][C:11]=1[C:20]([OH:22])=O.[CH:23]([O:25][CH2:26][CH2:27][O:28][NH2:29])=[CH2:24].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.CCN(C(C)C)C(C)C>CN(C=O)C>[CH:23]([O:25][CH2:26][CH2:27][O:28][NH:29][C:20]([C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][C:10]=1[NH:9][C:3]1[CH:4]=[CH:5][C:6]([I:8])=[CH:7][C:2]=1[F:1])[C:16](=[O:19])[NH:15][CH2:14]2)=[O:22])=[CH2:24]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 67079883HCID 67079883, compound

Product 1

HCID 86653626HCID 86653626, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-(2-Fluoro-4-iodo-phenylamino)-1-oxo-2,3-dihydro-1H-isoindole-5-carboxylic acid (209 mg, 0.52 mmol), O-(2-vinyloxy-ethyl)-hydroxylamine (58 mg, 0.56 mmol), HOBt (77 mg, 0.56 mmol), EDCI hydrochloride (109 mg, 0.56 mmol) and DIPEA (96 μL, 0.56 mmol) were dissolved in DMF (10 mL). The reaction mixture was stirred at room temperature for 16 hours then concentrated in vacuo. The resultant residue was dissolved in ethyl acetate (10 mL), washed with aqueous saturated sodium bicarbonate solution (10 mL) and the aqueous fraction extracted twice with ethyl acetate (2×10 mL). The combined organic fractions were washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0-10% methanol in DCM) to yield the title compound as a brown solid (100 mg, 40%). LCMS (Method B): RT=3.32 min, 2M+H+=995.

Workup

  1. concentrationthen concentrated in vacuo
  2. dissolutionThe resultant residue was dissolved in ethyl acetate (10 mL)
  3. washwashed with aqueous saturated sodium bicarbonate solution (10 mL)
  4. extractionthe aqueous fraction extracted twice with ethyl acetate (2×10 mL)
  5. washThe combined organic fractions were washed with brine (20 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-671a774b62e94a06b46888bee20f8a47
Source dataset
uspto-grants-2013_07
Patent number
US08492427B2

Reaction notes

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