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

HRID 2064035ノート

反応式

HRID 2064035 の反応式
[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]

参加物

7

反応物 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 591401305-(2-Fluoro-4-cyclopropylphenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-f59eab9d5cab4d16bc7b39f374becb0c
出典データセット
uspto-grants-2012_10
特許番号
US08288408B2

反応ノート

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