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Diisopropylethylamine → N-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-[1,4]oxazepan-4-yl-ethoxy)-phenyl]-3-fluoro-4-trifluoromethyl-benzamide

HRID 1626227
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HRID 1626227 반응식
[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH2:24])[CH:11]=[CH:12][C:13]=1[O:14][CH2:15][CH2:16][N:17]1[CH2:23][CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.C(N(CC)C(C)C)(C)C.[F:34][C:35]1[CH:36]=[C:37]([CH:41]=[CH:42][C:43]=1[C:44]([F:47])([F:46])[F:45])[C:38](Cl)=[O:39]>CC(N(C)C)=O.CS(C)=O>[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:24][C:38](=[O:39])[C:37]2[CH:41]=[CH:42][C:43]([C:44]([F:45])([F:46])[F:47])=[C:35]([F:34])[CH:36]=2)[CH:11]=[CH:12][C:13]=1[O:14][CH2:15][CH2:16][N:17]1[CH2:23][CH2:22][CH2:21][O:20][CH2:19][CH2:18]1
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참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 27347093-Fluoro-4-(trifluoromethyl)benzoyl chlorideHCID 589642603-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-[1,4]oxazepan-4-yl-ethoxy)-phenylamine

생성물 1

HCID 11556103N-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-[1,4]oxazepan-4-yl-ethoxy)-phenyl]-3-fluoro-4-trifluoromethyl-benzamide수율 53%

시약·촉매·용매 2

HCID 679
Dimethyl Sulfoxide
용매
HCID 31374Dimethylacetamide용매

실험 절차

To a solution of 3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-[1,4]oxazepan-4-yl-ethoxy)-phenylamine (0.06 g, 0.152 mmol), and N,N-diisopropylethylamine (0.0529 mL, 0.304 mmol) in 3.0 mL of DMA was added slowly 3-fluoro-4-(trifluoromethyl)benzoyl chloride (0.0278 mL, 0.182 mmol) and the reaction mixture was stirred at ambient temperature overnight. The reaction mixture was diluted to 5.0 mL with DMSO and subjected to purification on a RP-HPLC. The proper fractions were collected and lyophilized to furnish N-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-[1,4]oxazepan-4-yl-ethoxy)-phenyl]-3-fluoro-4-trifluoromethyl-benzamide as an off-white semisolid in 53% yield. LCMS m/z (%)=585 (M+H79Br, 100), 587 (M+H81Br, 98). 1H NMR (400 MHz, DMSO-d6) δ: 10.3 (bs, 1H), 8.06 (d, J=11.27 Hz, 1H), 7.95-8.01 (m, 3H), 7.72 (d, J=2.60 Hz, 1H), 7.68 (d, J=2.36 Hz, 1H), 7.31 (d. J=9.48 Hz, 1H), 4.35-4.44 (m, 2H), 3.5-3.9 (m, 10H), 2.51-2.69 (m, 5H).

후처리

  1. customsubjected to purification on a RP-HPLC
  2. customThe proper fractions were collected

출처 및 근거

ORD 기록
ord-56be631676dd4fb4a2eef9f5af4c34a3
출처 데이터셋
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08785441B2

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