Diisopropylethylamine → Ethyl 3-{4-methoxy-4-[(1-methylcyclobutyl)carbamoyl]piperidin-1-yl}-8-azabicyclo[3.2.1]octane-8-carboxylate

HRID 1777288ノート

反応式

HRID 1777288 の反応式
[CH2:1]([O:3][C:4]([N:6]1[CH:11]2[CH2:12][CH2:13][CH:7]1[CH2:8][CH:9]([N:14]1[CH2:19][CH2:18][C:17]([O:23][CH3:24])([C:20]([OH:22])=O)[CH2:16][CH2:15]1)[CH2:10]2)=[O:5])[CH3:2].Cl.[CH3:26][C:27]1([NH2:31])[CH2:30][CH2:29][CH2:28]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:24][O:23][C:17]1([C:20](=[O:22])[NH:31][C:27]2([CH3:26])[CH2:30][CH2:29][CH2:28]2)[CH2:16][CH2:15][N:14]([CH:9]2[CH2:8][CH:7]3[N:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH:11]([CH2:12][CH2:13]3)[CH2:10]2)[CH2:19][CH2:18]1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 183324491-Methylcyclobutan-1-amine hydrochlorideHCID 900796311-[8-(Ethoxycarbonyl)-8-azabicyclo[3.2.1]oct-3-yl]-4-methoxypiperidine-4-carboxylic acid

生成物 1

HCID 73438472Ethyl 3-{4-methoxy-4-[(1-methylcyclobutyl)carbamoyl]piperidin-1-yl}-8-azabicyclo[3.2.1]octane-8-carboxylate収率 25.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

1-[8-(Ethoxycarbonyl)-8-azabicyclo[3.2.1]oct-3-yl]-4-methoxypiperidine-4-carboxylic acid (0.093 g, assumed 0.27 mmol) was dissolved in DMF (5 mL) and (1-methylcyclobutyl)amine hydrochloride (0.05 g, 0.411 mmol), HATU (0.156 g, 0.41 mmol) and DIPEA (0.177 g, 0.24 mL, 1.37 mmol) were added. The reaction mixture was stirred at rt for 60 h and the solvents were removed in vacuo. The residue was partitioned between DCM and sat. NaHCO3 sol., the organic layer was washed with sat. NaCl sol. and dried (MgSO4). The solvents were removed in vacuo, and the residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 10 g, 40-63 μm, 60 A, 25 mL per min, gradient 0% to 10% MeOH in DCM]) to give ethyl 3-{4-methoxy-4-[(1-methylcyclobutyl)carbamoyl]piperidin-1-yl}-8-azabicyclo[3.2.1]octane-8-carboxylate isomer 1 (0.028 g, 25%) as a pale yellow gum.

後処理

  1. customthe solvents were removed in vacuo
  2. customThe residue was partitioned between DCM and sat. NaHCO3 sol.
  3. washthe organic layer was washed with sat. NaCl sol.
  4. dry with materialdried (MgSO4)
  5. customThe solvents were removed in vacuo
  6. customthe residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 10 g, 40-63 μm, 60 A, 25 mL per min, gradient 0% to 10% MeOH in DCM])

出典と根拠

ORDレコード
ord-ef0247b7cc984c46bf3b8ba233114902
出典データセット
uspto-grants-2016_02
特許番号
US09266857B2

反応ノート

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