Dimethylformamide → Ethyl 2-{4-[(2-methylpropyl)carbamoyl]piperidin-1-yl}-6-azaspiro[3.4]octane-6-carboxylate

HRID 1777303ノート

反応式

HRID 1777303 の反応式
[CH2:1]([O:3][C:4]([N:6]1[CH2:22][CH2:21][C:8]2([CH2:11][CH:10]([N:12]3[CH2:17][CH2:16][CH:15]([C:18](O)=[O:19])[CH2:14][CH2:13]3)[CH2:9]2)[CH2:7]1)=[O:5])[CH3:2].C[N:24]([CH:26]=O)C.CN(C(ON1N=N[C:38]2[CH:39]=CC=N[C:37]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>>[CH3:37][CH:38]([CH3:39])[CH2:26][NH:24][C:18]([CH:15]1[CH2:14][CH2:13][N:12]([CH:10]2[CH2:9][C:8]3([CH2:21][CH2:22][N:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:7]3)[CH2:11]2)[CH2:17][CH2:16]1)=[O:19]

参加物

5

反応物 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 900796681-[6-(Ethoxycarbonyl)-6-azaspiro[3.4]oct-2-yl]piperidine-4-carboxylic acid

生成物 1

HCID 73438536Ethyl 2-{4-[(2-methylpropyl)carbamoyl]piperidin-1-yl}-6-azaspiro[3.4]octane-6-carboxylate収率 37.7%

実験手順

1-[6-(Ethoxycarbonyl)-6-azaspiro[3.4]oct-2-yl]piperidine-4-carboxylic acid (0.200 g, 0.65 mmol) was dissolved in DMF (5 mL) isobutylamine (0.071 g, 0.97 mmol), HATU (0.270 g, 0.71 mmol) and DIPEA (0.417 g, 3.23 mmol) were added. The reaction mixture was stirred at rt overnight under nitrogen. The solvents were removed in vacuo, and the residue was partitioned between DCM and sat. NaHCO3 sol., organic layer washed with sat. NaCl sol. and dried over MgSO4. The solvents were removed in vacuo, and the residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 25 g, 40-63 μm, 60 A, 12 mL per min, gradient 0% to 10% MeOH in DCM]) to give ethyl 2-{4-[(2-methylpropyl)carbamoyl]piperidin-1-yl}-6-azaspiro[3.4]octane-6-carboxylate (0.089 g, 37.7%) as a pale yellow gum as a mixture of diastereomers.

後処理

  1. customThe solvents were removed in vacuo
  2. customthe residue was partitioned between DCM and sat. NaHCO3 sol., organic layer
  3. washwashed with sat. NaCl sol.
  4. dry with materialdried over MgSO4
  5. customThe solvents were removed in vacuo
  6. customthe residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 25 g, 40-63 μm, 60 A, 12 mL per min, gradient 0% to 10% MeOH in DCM])

出典と根拠

ORDレコード
ord-33cc9767f0a346018e25aa28ffada92f
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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