Triethylamine → 1-methylcyclopropyl 4-((1R,2S)-2-(2-(4-(1H-tetrazol-1-yl)phenoxy)ethyl)cyclopropyl)piperidine-1-carboxylate

HRID 1850735ノート

反応式

HRID 1850735 の反応式
[N:1]1([C:6]2[CH:30]=[CH:29][C:9]([O:10][CH2:11][CH2:12][C@@H:13]3[CH2:15][C@@H:14]3[CH:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][CH2:25][CH:26](C)[CH3:27])=[O:23])[CH2:18][CH2:17]3)=[CH:8][CH:7]=2)[CH:5]=[N:4][N:3]=[N:2]1.[CH2:31](N(CC)CC)C.C(=O)(OC1(C)CC1)ON1C(=O)CCC1=O>ClCCl>[N:1]1([C:6]2[CH:30]=[CH:29][C:9]([O:10][CH2:11][CH2:12][C@@H:13]3[CH2:15][C@@H:14]3[CH:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]4([CH3:31])[CH2:26][CH2:27]4)=[O:23])[CH2:18][CH2:17]3)=[CH:8][CH:7]=2)[CH:5]=[N:4][N:3]=[N:2]1

参加物

5

反応物 3

HCID 8471TriethylamineHCID 577528092,5-Dioxopyrrolidin-1-yl 1-methylcyclopropyl carbonateHCID 66563045isobutyl 4-((1R,2S)-2-(2-(4-(1H-tetrazol-1-yl)phenoxy)ethyl)cyclopropyl)piperidine-1-carboxylate

生成物 1

HCID 665631411-methylcyclopropyl 4-((1R,2S)-2-(2-(4-(1H-tetrazol-1-yl)phenoxy)ethyl)cyclopropyl)piperidine-1-carboxylate

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

4-((1R,2S)-2-(2-(4-(1H-Tetrazol-1-yl)phenoxy)ethyl)cyclopropyl)piperidine (Step B, Example 1; 100 mg, 0.319 mmol) and triethylamine (97 mg, 0.96 mmol) were dissolved in dichloromethane (5 mL). 2,5-Dioxopyrrolidin-1-yl 1-methylcyclopropyl carbonate (81 mg, 0.38 mmol) was added. The mixture was stirred at RT for 30 min and concentrated to dryness under reduced pressure. The residue was purified by silica gel chromatography (12 g RediSep, eluted with dichloromethane/methanol, 199:1, 1 L). The product containing fractions were combined and concentrated under reduced pressure. The compound was further purified by prep-HPLC (SunFire C18 OBD, 10 μm, 50×150 mm, 118 mL/min, acetonitrile/water 10:90 to 90:10 at 25 min, total run 30 min) to provide the title compound as an off-white solid. 1H NMR (300 MHz, CDCl3) δ 8.90 (s, 1H), 7.59 (d, J=9.0 Hz, 2H), 7.07 (d, J=9.0 Hz, 2H), 4.30-3.90 (m, 4H), 2.80-2.60 (m, 2H), 2.25-2.10 (m, 1H), 1.85-1.70 (m, 2H), 1.60-1.45 (m, 1H), 1.55 (s, 3H), 1.40-1.20 (m, 2H), 1.10-0.80 (m, 4H), 0.80-0.55 (m, 4H), −0.09 (q, J=5.2 Hz, 1H). MS (ESI) m/z 412 [M+H]+.

後処理

  1. concentrationconcentrated to dryness under reduced pressure
  2. customThe residue was purified by silica gel chromatography (12 g RediSep, eluted with dichloromethane/methanol, 199:1, 1 L)
  3. additionThe product containing fractions
  4. concentrationconcentrated under reduced pressure
  5. customThe compound was further purified by prep-HPLC (SunFire C18 OBD, 10 μm, 50×150 mm, 118 mL/min, acetonitrile/water 10:90 to 90:10 at 25 min, total run 30 min)

出典と根拠

ORDレコード
ord-b7ed8f9d0cad4f64903ffda56cdc1785
出典データセット
uspto-grants-2015_02
特許番号
US08957062B2

反応ノート

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