Triethylamine → 1'-(3-bromo-1H-pyrrolo[3,2-b]pyridine-6-carbonyl)-2-tert-butyl-4,6-dihydrospiro[indazole-5,4'-piperidin]-7(2H)-one

HRID 2403703ノート

反応式

HRID 2403703 の反応式
Cl.[Br:2][C:3]1[C:7]2=[N:8][CH:9]=[C:10]([C:12]([OH:14])=O)[CH:11]=[C:6]2[NH:5][CH:4]=1.Cl.[C:16]([N:20]1[CH:33]=[C:32]2[C:22]([C:23](=[O:34])[CH2:24][C:25]3([CH2:31]2)[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)=[N:21]1)([CH3:19])([CH3:18])[CH3:17].C(N(CC)CC)C.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>ClCCl.C(OCC)(=O)C.CN(C)C=O>[Br:2][C:3]1[C:7]2=[N:8][CH:9]=[C:10]([C:12]([N:28]3[CH2:27][CH2:26][C:25]4([CH2:24][C:23](=[O:34])[C:22]5[C:32](=[CH:33][N:20]([C:16]([CH3:19])([CH3:18])[CH3:17])[N:21]=5)[CH2:31]4)[CH2:30][CH2:29]3)=[O:14])[CH:11]=[C:6]2[NH:5][CH:4]=1

参加物

9

反応物 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 573370712-tert-butyl-4,6-dihydrospiro[indazole-5,4'-piperidin]-7(2H)-one hydrochloride saltHCID 708961403-bromo-1H-pyrrolo[3,2-b]pyridine-6-carboxylic acid hydrochloride

生成物 1

HCID 708961201'-(3-bromo-1H-pyrrolo[3,2-b]pyridine-6-carbonyl)-2-tert-butyl-4,6-dihydrospiro[indazole-5,4'-piperidin]-7(2H)-one収率 71%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a suspension of 3-bromo-1H-pyrrolo[3,2-b]pyridine-6-carboxylic acid hydrochloride (2.75 g, 9.91 mmol) and 2-tert-butyl-4,6-dihydrospiro[indazole-5,4′-piperidin]-7(2H)-one hydrochloride salt (2.95 g, 9.91 mmol) in dichloromethane (30 mL) was added triethylamine (5.52 mL, 39.6 mmol). N,N-dimethylformamide (5 mL) was then added, followed by 1-hydroxybenzotriazole (1.61 g, 11.9 mmol) and 1, (3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (2.28 g, 11.9 mmol). The reaction was allowed to stir at room temperature for 60 hours. The reaction was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate and brine. The organics were dried over magnesium sulfate, filtered, and concentrated. Purification by flash column chromatography (0-10% methanol/ethyl acetate) gave the title compound (3.39 g, 71%) as a pale brown solid. +ESI (M+1+H) 486.2; 1H NMR (400 MHz, CDCl3, δ): 10.05 (br. s., 1 H), 8.57 (d, J=1.8 Hz, 1 H), 7.87 (d, J=1.8 Hz, 1 H), 7.61 (d, J=2.7 Hz, 1 H), 7.44 (s, 1 H), 3.78 (br. s., 2 H), 3.51 (br. s., 2 H), 2.81 (s, 2 H), 2.65 (s, 2 H), 1.63 (s, 13 H).

後処理

  1. washwashed with saturated aqueous sodium bicarbonate and brine
  2. dry with materialThe organics were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by flash column chromatography (0-10% methanol/ethyl acetate)

出典と根拠

ORDレコード
ord-4dde3c4bb6c84ede8409b522d1d911d4
出典データセット
uspto-grants-2014_08
特許番号
US08802688B2

反応ノート

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