Hydrochloric Acid → N-(2-Fluoro-5-(6-oxo-5-(5-(2-oxopiperazin-1-yl)pyridin-2-ylamino)-1,6-dihydropyridazin-3-yl)phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide

HRID 1907812ノート

反応式

HRID 1907812 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([NH:15][C:16]3[N:21]=[CH:20][C:19]([N:22]4[CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][C:23]4=[O:35])=[CH:18][CH:17]=3)[C:11](=[O:14])[NH:12][N:13]=2)=[CH:4][C:3]=1[NH:36][C:37]([C:39]1[S:43][C:42]2[CH2:44][CH2:45][CH2:46][CH2:47][C:41]=2[CH:40]=1)=[O:38].CO.Cl.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([NH:15][C:16]3[CH:17]=[CH:18][C:19]([N:22]4[CH2:27][CH2:26][NH:25][CH2:24][C:23]4=[O:35])=[CH:20][N:21]=3)[C:11](=[O:14])[NH:12][N:13]=2)=[CH:4][C:3]=1[NH:36][C:37]([C:39]1[S:43][C:42]2[CH2:44][CH2:45][CH2:46][CH2:47][C:41]=2[CH:40]=1)=[O:38]

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 11430Potassium CarbonateHCID 58539996tert-Butyl 4-(6-(6-(4-Fluoro-3-(4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamido)phenyl)-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)-3-oxopiperazine-1-carboxylate

生成物 1

HCID 58540158N-(2-Fluoro-5-(6-oxo-5-(5-(2-oxopiperazin-1-yl)pyridin-2-ylamino)-1,6-dihydropyridazin-3-yl)phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide収率 56%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

実験手順

A 10-mL single-neck round bottomed flask equipped with a magnetic stirrer was purged with nitrogen and charged with 2h (75 mg, 0.129 mmol), methanol (2 mL) and 4 M HCl in dioxane (2 mL) and the mixture stirred for 2 h. After this time, ethyl acetate (20 mL) and water (20 mL) were added. The pH was adjusted to 6.5 with aqueous 10% potassium carbonate. The aqueous layer was separated and extracted with ethyl acetate (2×25 mL). The combined organic layers were washed with brine (20 mL) and dried over sodium sulfate. The drying agent was removed by filtration. The filtrate was concentrated under reduced pressure to a residue which was purified by column chromatography to afford a 56% yield of 21 (40 mg) as a white solid: mp 285-287° C.; 1H NMR (500 MHz, DMSO-d6) δ13.21 (s, 1H), 10.07 (s, 1H), 9.50 (s, 1H), 8.36 (d, 1H, J=2.5 Hz), 8.04 (dd, 1H, J=7.5, 2.0 Hz), 7.71 (s, 1H), 7.70 (m, 1H), 7.65 (m, 1H), 7.53 (d, 1H, =9.0 Hz), 7.41 (t, 1H, J=9.0 Hz), 3.63 (t, 2H, J=5.5 Hz), 3.42 (s, 2H), 3.04 (t, 2H, J=5.0 Hz), 2.78 (t, 2H, J=5.0 Hz), 2.62 (t, 2H, J=5.5 Hz), 1.78 (m, 4H); MS (ESI+) m/z 560.0 (M+H).

後処理

  1. customA 10-mL single-neck round bottomed flask equipped with a magnetic stirrer
  2. customwas purged with nitrogen
  3. customThe aqueous layer was separated
  4. extractionextracted with ethyl acetate (2×25 mL)
  5. washThe combined organic layers were washed with brine (20 mL)
  6. dry with materialdried over sodium sulfate
  7. customThe drying agent was removed by filtration
  8. concentrationThe filtrate was concentrated under reduced pressure to a residue which
  9. customwas purified by column chromatography

出典と根拠

ORDレコード
ord-0ea72364584c4c1f8e0a8be89a5ae66a
出典データセット
uspto-grants-2013_12
特許番号
US08598174B2

反応ノート

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