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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
Notes
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Reaction equation

HRID 1626227 reaction equation
[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
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 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

Product 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-benzamideYield 53%

Reagents, catalysts & solvents 2

HCID 679
Dimethyl Sulfoxide
Solvent
HCID 31374DimethylacetamideSolvent

Procedure

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).

Workup

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

Sources & evidence

ORD record
ord-56be631676dd4fb4a2eef9f5af4c34a3
Source dataset
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08785441B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes