1-Hydroxybenzotriazole → 5-(4-Cyclopropyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (2-vinyloxy-ethoxy)-amide

HRID 2064035Notes

Reaction equation

HRID 2064035 reaction equation
[CH:1]1([C:4]2[CH:9]=[CH:8][C:7]([NH:10][C:11]3[N:16]4[CH:17]=[N:18][CH:19]=[C:15]4[CH:14]=[CH:13][C:12]=3[C:20](O)=[O:21])=[C:6]([F:23])[CH:5]=2)[CH2:3][CH2:2]1.[CH:24]([O:26][CH2:27][CH2:28][O:29][NH2:30])=[CH2:25].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:24]([O:26][CH2:27][CH2:28][O:29][NH:30][C:20]([C:12]1[CH:13]=[CH:14][C:15]2[N:16]([CH:17]=[N:18][CH:19]=2)[C:11]=1[NH:10][C:7]1[CH:8]=[CH:9][C:4]([CH:1]2[CH2:2][CH2:3]2)=[CH:5][C:6]=1[F:23])=[O:21])=[CH2:25]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 59140130HCID 59140130, compound

Product 1

HCID 591401465-(4-Cyclopropyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (2-vinyloxy-ethoxy)-amideYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 5-(4-cyclopropyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (400 mg, 1.29 mmol), O-(2-vinyloxyethyl)-hydroxylamine (265 mg, 2.57 mmol) and HOBt (225 mg, 1.67 mmol) in DMF (5 mL) was added EDCI hydrochloride (320 mg, 1.67 mmol), and DIPEA (0.290 mL, 1.67 mmol) before the reaction mixture was stirred at room temperature for 18 hours. The products were partitioned between ethyl acetate and saturated aqueous NaHCO3, the organic layer separated and washed with brine then dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0-35% ethyl acetate in cylcohexane) to give the title compound (270 mg, 53%). LCMS (Method B): RT 2.79 [M+H]+397.

Workup

  1. customThe products were partitioned between ethyl acetate and saturated aqueous NaHCO3
  2. customthe organic layer separated
  3. washwashed with brine
  4. dry with materialthen dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f59eab9d5cab4d16bc7b39f374becb0c
Source dataset
uspto-grants-2012_10
Patent number
US08288408B2

Reaction notes

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