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

HRID 2064033
ノート
印刷プレビュー

反応式

HRID 2064033 の反応式
C([O:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[N:11]=[CH:12][C:13]2[N:14]([CH:25]=[N:26][CH:27]=2)[C:15]=1[NH:16][C:17]1[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=1[F:24])=[O:9])=C.Cl.O1CCOCC1>CO.ClCCl>[OH:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[N:11]=[CH:12][C:13]2[N:14]([CH:25]=[N:26][CH:27]=2)[C:15]=1[NH:16][C:17]1[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=1[F:24])=[O:9]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 591401785-(2-Fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyrazine-6-carboxylic acid (2-vinyloxy-ethoxy)-amide

生成物 1

HCID 441359785-(2-Fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyrazine-6-carboxylic acid (2-hydroxy-ethoxy)-amide収率 51%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒
HCID 6344
Dichloromethane
溶媒

実験手順

To a solution of 5-(2-fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyrazine-6-carboxylic acid (2-vinyloxy-ethoxy)-amide (24.0 mg, 0.05 mmol) in methanol (0.5 mL) and dichloromethane (1.0 mL) was added 4M HCl in 1,4-dioxane (30 μL, 0.1 mmol, 2.5 eq.), and the reaction was stirred at ambient temperature under N2 for 2 h. The reaction mixture was concentrated in vacuo then poured into ethyl acetate. The organic layer was washed with a saturated solution of sodium bicarbonate, 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 25%, methanol in dichloromethane) to afford the title compound as yellow solid (11.6 mg, 51%). 1H NMR (MeOD, 400 MHz) δ ppm 8.74 (s, 1H), 7.87 (s, 1H), 7.84 (s, 1H), 7.62 (dd, J=10.20, 1.82 Hz, 1H), 7.48 (d, J=8.41 Hz, 1H), 6.61 (t, J=8.53 Hz, 1H), 4.05 (t, J=4.80 Hz, 2H), 3.78 (t, J=4.80 Hz, 2H)); LCMS (method E1): RT=4.33 min, [M+H]+=458.

後処理

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additionthen poured into ethyl acetate
  3. washThe organic layer was washed with a saturated solution of sodium bicarbonate, water, and brine
  4. customThe organic phase was isolated
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-a9bd644ae4384a28947ea1ae3a0b8085
出典データセット
uspto-grants-2012_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08288408B2

反応ノート

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