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Methyl iodide → 5'-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2'-(isopropoxymethyl)-N,N-dimethylbiphenyl-4-carboxamide

HRID 39178
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HRID 39178 반응식
[H-].[Na+].[O:3]1[C:7]2[CH:8]=[CH:9][C:10]([C:12]3([C:15]([NH:17][C:18]4[CH:19]=[CH:20][C:21]([CH3:35])=[C:22]([C:24]5[CH:29]=[CH:28][C:27]([C:30]([N:32]([CH3:34])[CH3:33])=[O:31])=[CH:26][CH:25]=5)[CH:23]=4)=[O:16])[CH2:14][CH2:13]3)=[CH:11][C:6]=2[O:5][CH2:4]1.IC>O1CCCC1.CN(C)C=O>[O:3]1[C:7]2[CH:8]=[CH:9][C:10]([C:12]3([C:15]([NH:17][C:18]4[CH:19]=[CH:20][C:21]([CH2:35][O:3][CH:7]([CH3:8])[CH3:6])=[C:22]([C:24]5[CH:25]=[CH:26][C:27]([C:30]([N:32]([CH3:34])[CH3:33])=[O:31])=[CH:28][CH:29]=5)[CH:23]=4)=[O:16])[CH2:14][CH2:13]3)=[CH:11][C:6]=2[O:5][CH2:4]1
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참가 물질

6

반응물 3

HCID 6328Methyl iodide2회HCID 24758Sodium hydride2회HCID 592065844-[5-(1-benzo[1,3]dioxol-5-ylcyclopropyl)carbonylamino-2-methyl-phenyl]-N,N-dimethyl-benzamide

생성물 1

HCID 592066525'-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2'-(isopropoxymethyl)-N,N-dimethylbiphenyl-4-carboxamide수율 75.7%

시약·촉매·용매 2

HCID 6228
Dimethylformamide
용매
HCID 8028Tetrahydrofuran용매

실험 절차

Sodium hydride (2.2 mg, 0.055 mmol, 60% by weight dispersion in oil) was slowly added to a stirred solution of 5′(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-N,N,2′-trimethylbiphenyl-4-carboxamide (21 mg, 0.048 mmol) in a mixture of 0.90 mL of anhydrous tetrahydrofuran (THF) and 0.10 mL of anhydrous N,N-dimethylformamide (DMF). The resulting suspension was allowed to stir for 3 minutes before iodomethane (0.0048 mL, 0.072 mmol) was added to the reaction mixture. An additional aliquot of sodium hydride and iodomethane were required to consume all of the starting material which was monitored by LCMS. The crude reaction product was evaporated to dryness, redissolved in a minimum of DMF and purified by preparative LCMS chromatography to yield 5′-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-2′-(isopropoxymethyl)-N,N-dimethylbiphenyl-4-carboxamide (9.1 mg, 42%) ESI-MS m/z calc. 456.2, found 457.5 (M+1)+. Retention time of 2.94 minutes. 1H-NMR (400 MHz, CD3CN) δ 0.91-0.93 (m, 2H), 1.41-1.45 (m, 2H), 2.23 (s, 3H), 3.00 (s, 3H), 3.07 (s, 3H), 3.20 (s, 3H), 5.81 (s, 2H), 6.29-6.36 (m, 2H), 6.56 (d, J=8.0 Hz, 1H), 6.69 (s, 1H), 6.92 (dd, J=1.6, 7.9 Hz, 1H), 7.17 (d, J=8.1 Hz, 1H), 7.28 (d, J=8.1 Hz, 2H), 7.46 (dd, J=1.8, 6.4 Hz, 2H).

후처리

  1. additionwas added to the reaction mixture
  2. customto consume all of the starting material which
  3. customThe crude reaction product
  4. customwas evaporated to dryness
  5. dissolutionredissolved in a minimum of DMF
  6. custompurified by preparative LCMS chromatography

출처 및 근거

ORD 기록
ord-20c6adca01234c00865c95a81a49209c
출처 데이터셋
uspto-grants-2013_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08524767B2

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