Hydroxylamine → 8-(4-Cyclopropyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-vinyloxy-ethoxy)-amide

HRID 2067012노트

반응식

HRID 2067012 반응식
CO[C:3]([C:5]1[CH:10]=[CH:9][N:8]2[CH:11]=[N:12][CH:13]=[C:7]2[C:6]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH:21]2[CH2:23][CH2:22]2)=[CH:17][C:16]=1[F:24])=[O:4].[OH-:25].[Na+].[NH2:27][OH:28].[CH3:29][CH2:30]N=C=NCCCN(C)C.[CH:40]1C=CC2N(O)N=NC=2[CH:45]=1>C(OCC)(=O)C>[CH:29]([O:25][CH2:40][CH2:45][O:28][NH:27][C:3]([C:5]1[CH:10]=[CH:9][N:8]2[CH:11]=[N:12][CH:13]=[C:7]2[C:6]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH:21]2[CH2:23][CH2:22]2)=[CH:17][C:16]=1[F:24])=[O:4])=[CH2:30]

참가 물질

7

반응물 5

HCID 787HydroxylamineHCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 595651918-(4-Cyclopropyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester

생성물 1

HCID 595652268-(4-Cyclopropyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid (2-vinyloxy-ethoxy)-amide수율 67.3%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

반응 조건

온도
65 °C

실험 절차

To a solution of 8-(4-cyclopropyl-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester (68 mg, 0.21 mmol) in IMS (2.5 mL) was added a 1.0 M aqueous solution of sodium hydroxide (0.25 mL, 0.25 mmol). The reaction mixture was heated at 65° C. for 1 hour and then cooled to room temperature and concentrated in vacuo. The resulting residue was azeotroped with toluene, and then suspended in THF (4 mL). 042-Vinyloxy-ethyl)-hydroxylamine (43 mg, 0.42 mmol), N-N-diisopropylethylamine (0.14 mL, 0.84 mmol), EDCI (81 mg, 0.42 mmol) and HOBt (57 mg, 0.42 mmol) were then added sequentially, before the reaction mixture was stirred for 18 hours at room temperature. The reaction mixture was then diluted with ethyl acetate and washed with water, a saturated aqueous solution of sodium bicarbonate and brine before being dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0% to 5%, methanol in dichloromethane) to afford the title compound as a pale yellow oil (56 mg, 67%). LCMS (method B): RT=3.02 min, [M+H]+=397.

후처리

  1. temperaturecooled to room temperature
  2. concentrationconcentrated in vacuo
  3. customThe resulting residue was azeotroped with toluene
  4. washwashed with water
  5. dry with materiala saturated aqueous solution of sodium bicarbonate and brine before being dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-c134055e6b6648d0af0bd8be6d526e9f
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08293763B2

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