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

HRID 1500730노트

반응식

HRID 1500730 반응식
[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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-0a44c40a48e2495ab0f68d83d79e79f0
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09206174B2

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