Diisopropylethylamine → 5-(2-Fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyrazine-6-carboxylic acid (2-vinyloxy-ethoxy)-amide

HRID 1500727Notes

Reaction equation

HRID 1500727 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[N:15]2[CH:16]=[N:17][CH:18]=[C:14]2[CH:13]=[N:12][C:11]=1[C:19]([OH:21])=O.[CH:22]([O:24][CH2:25][CH2:26][O:27][NH2:28])=[CH2:23].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>CN(C=O)C.C(OCC)(=O)C>[CH:22]([O:24][CH2:25][CH2:26][O:27][NH:28][C:19]([C:11]1[N:12]=[CH:13][C:14]2[N:15]([CH:16]=[N:17][CH:18]=2)[C:10]=1[NH:9][C:3]1[CH:4]=[CH:5][C:6]([I:8])=[CH:7][C:2]=1[F:1])=[O:21])=[CH2:23]

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 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 591401265-(2-Fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyrazine-6-carboxylic acid

Product 1

HCID 591401785-(2-Fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyrazine-6-carboxylic acid (2-vinyloxy-ethoxy)-amideYield 18%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-(2-fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyrazine-6-carboxylic acid (110 mg, 0.28 mmol), O-(2-vinyloxy-ethyl)-hydroxylamine (45.6 mg, 0.44 mmol, 1.6 eq.), HATU (157.6 mg, 0.41 mmol, 1.5 eq.), and DIPEA (96.0 μL, 0.55 mmol, 2.0 eq.) in anhydrous DMF (4.2 mL) was stirred for 18 hours under N2 at ambient temperature. The reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous solution of sodium bicarbonate followed by water and brine. The organic phase was isolated, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0% to 15%, methanol in dichloromethane) to afford the desired product as a yellow solid (24 mg, 18%). LCMS (method D1): RT=1.00 min, [M+H]+=484.

Workup

  1. washwashed with a saturated aqueous solution of sodium bicarbonate
  2. customThe organic phase was isolated
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c6d31f98489749e18d4cc33df398c6ac
Source dataset
uspto-grants-2015_12
Patent number
US09206174B2

Reaction notes

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