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1-Hydroxybenzotriazole → 6-(5-bromopyridin-3-yl)-1'-[(1-cyclopropyl-4-methoxy-3-methyl-1H-indol-6-yl)carbonyl]spiro[chroman-2,4'-piperidin]-4-one

HRID 420132
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HRID 420132 반응식
[CH:1]1([N:4]2[C:12]3[C:7](=[C:8]([O:16][CH3:17])[CH:9]=[C:10]([C:13]([OH:15])=O)[CH:11]=3)[C:6]([CH3:18])=[CH:5]2)[CH2:3][CH2:2]1.Cl.Cl.[Br:21][C:22]1[CH:23]=[C:24]([C:28]2[CH:29]=[C:30]3[C:40](=[CH:41][CH:42]=2)[O:39][C:33]2([CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)[CH2:32][C:31]3=[O:43])[CH:25]=[N:26][CH:27]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>C(OCC)(=O)C.CN(C=O)C.C(N(CC)CC)C>[Br:21][C:22]1[CH:23]=[C:24]([C:28]2[CH:29]=[C:30]3[C:40](=[CH:41][CH:42]=2)[O:39][C:33]2([CH2:34][CH2:35][N:36]([C:13]([C:10]4[CH:11]=[C:12]5[C:7]([C:6]([CH3:18])=[CH:5][N:4]5[CH:1]5[CH2:2][CH2:3]5)=[C:8]([O:16][CH3:17])[CH:9]=4)=[O:15])[CH2:37][CH2:38]2)[CH2:32][C:31]3=[O:43])[CH:25]=[N:26][CH:27]=1
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참가 물질

8

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 569716581-cyclopropyl-4-methoxy-3-methyl-1H-indole-6-carboxylic acidHCID 666493846-(5-Bromo-3-pyridinyl)spiro-[chroman-2,4'-piperidin]-4-one dihydrochloride

생성물 1

HCID 24966800
6-(5-bromopyridin-3-yl)-1'-[(1-cyclopropyl-4-methoxy-3-methyl-1H-indol-6-yl)carbonyl]spiro[chroman-2,4'-piperidin]-4-one

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 8471Triethylamine용매HCID 8857Ethyl Acetate용매

실험 절차

Triethylamine (0.33 mL) was added to a DMF (7.5 mL) solution of 1-cyclopropyl-4-methoxy-3-methyl-1H-indole-6-carboxylic acid (147 mg), 6-(5-bromo-3-pyridinyl)spiro-[chroman-2,4′-piperidin]-4-one dihydrochloride (268 mg), WSC hydrochloride (164 mg) and HOBT (110 mg), and stirred at r.t. for 5 h. This reaction mixture was diluted with ethyl acetate, then washed with water, aqueous saturated sodium bicarbonate and saturated saline water in that order, and dried with sodium sulfate. This was filtered, concentrated, and purified through silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound as a colorless amorphous substance. 1H-NMR (400 MHz, DMSO-d6) δ: 8.86 (1H, d, J=2.0 Hz), 8.66 (1H, d, J=2.0 Hz), 8.36 (1H, t, J=2.0 Hz), 8.05-7.99 (2H, m), 7.24 (1H, d, J=8.6 Hz), 7.13 (1H, s), 7.00 (1H, s), 6.50 (1H, s), 4.40-4.08 (1H, br m), 3.83 (3H, s), 3.78-3.22 (4H, br m), 2.94 (2H, s), 2.31 (3H, s), 2.04-1.75 (4H, br m), 1.03-0.97 (2H, m), 0.89-0.84 (2H, m); MS [M+H]+=600, 602.

후처리

  1. washwashed with water, aqueous saturated sodium bicarbonate and saturated saline water in that order
  2. dry with materialdried with sodium sulfate
  3. filtrationThis was filtered
  4. concentrationconcentrated
  5. custompurified through silica gel column chromatography (hexane/ethyl acetate)

출처 및 근거

ORD 기록
ord-7333ecd556b34a4a942bb2c83a270d25
출처 데이터셋
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08093389B2

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