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1,4-Dioxane hydrochloride → (1-Amino-cyclopropyl)-{3-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-azetidin-1-yl}-methanone

HRID 708162
ノート
印刷プレビュー

反応式

HRID 708162 の反応式
C(OC(=O)[NH:7][C:8]1([C:11]([N:13]2[CH2:16][CH:15]([C:17]3[CH:38]=[CH:37][C:20]4[C:21]5[N:22]=[C:23]([C:29]6[N:30]([CH:34]([CH3:36])[CH3:35])[N:31]=[CH:32][N:33]=6)[S:24][C:25]=5[CH2:26][CH2:27][O:28][C:19]=4[CH:18]=3)[CH2:14]2)=[O:12])[CH2:10][CH2:9]1)(C)(C)C.Cl.O1CCOCC1>CO>[NH2:7][C:8]1([C:11]([N:13]2[CH2:16][CH:15]([C:17]3[CH:38]=[CH:37][C:20]4[C:21]5[N:22]=[C:23]([C:29]6[N:30]([CH:34]([CH3:36])[CH3:35])[N:31]=[CH:32][N:33]=6)[S:24][C:25]=5[CH2:26][CH2:27][O:28][C:19]=4[CH:18]=3)[CH2:14]2)=[O:12])[CH2:9][CH2:10]1
参加物実験手順後処理出典と根拠反応ノート

参加物

4

反応物 2

HCID 204431481,4-Dioxane hydrochlorideHCID 67050572(1-{3-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-azetidine-1-carbonyl}-cyclopropyl)-carbamic acid tert-butyl ester

生成物 1

HCID 58203965(1-Amino-cyclopropyl)-{3-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-azetidin-1-yl}-methanone収率 59%

試薬・触媒・溶媒 1

HCID 887
Methanol
溶媒

実験手順

To a suspension of (1-{3-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-azetidine-1-carbonyl}-cyclopropyl)-carbamic acid tert-butyl ester (225 mg, 0.41 mmol) in MeOH (3.1 mL) was added 4N HCl/dioxan (1.0 mL, 4.1 mmol) and the reaction mixture was stirred for 18 hours. The resulting solid was filtered off and washed with diethyl ether before being partitioned between DCM and an aqueous saturated sodium bicarbonate solution. The phases were separated and the aqueous phase was extracted with DCM (×2). The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated in vacuo. The resultant residue was purified by flash chromatography (SiO2, 0-8% 2N NH3/MeOH in DCM). The resulting solid was suspended in ether and collected by filtration to give 425 as a white solid (108 mg, 59%). LCMS: RT=7.96 min, [M+H]+=451. 1H NMR δ (ppm) (DMSO-d6): 8.35 (1H, d, J=8.20 Hz), 8.02 (1H, s), 7.20 (1H, dd, J=8.22, 1.81 Hz), 7.05 (1H, s), 5.86-5.78 (1H, m), 4.59 (2H, t, J=9.01 Hz), 4.40 (2H, t, J=5.07 Hz), 4.20 (2H, d, J=7.67 Hz), 3.85 (1H, t, J=7.50 Hz), 3.44 (2H, t, J=5.08 Hz), 2.18 (2H, s), 1.58 (6H, d, J=6.59 Hz), 1.09-1.06 (2H, m), 0.70 (2H, q, J=3.28 Hz)

後処理

  1. filtrationThe resulting solid was filtered off
  2. washwashed with diethyl ether
  3. custombefore being partitioned between DCM
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted with DCM (×2)
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe resultant residue was purified by flash chromatography (SiO2, 0-8% 2N NH3/MeOH in DCM)
  10. filtrationcollected by filtration

出典と根拠

ORDレコード
ord-ae898e7be7e64049ab62d3c80dd14fcb
出典データセット
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09175009B2

反応ノート

読み込み中…

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