Diisopropylethylamine → N-[4-(2-Amino-2-methyl-propoxy)-3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-3-trifluoromethoxy-benzamide

HRID 1183918Notes

Reaction equation

HRID 1183918 reaction equation
[F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[C:7](Cl)=[O:8].[Br:15][C:16]1[CH:20]=[N:19][N:18]([CH3:21])[C:17]=1[C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][C:28]=1[O:29][CH2:30][C:31]([CH3:36])([N+:33]([O-])=O)[CH3:32])[NH2:25].C(N(CC)C(C)C)(C)C>ClCCl>[NH2:33][C:31]([CH3:36])([CH3:32])[CH2:30][O:29][C:28]1[CH:27]=[CH:26][C:24]([NH:25][C:7](=[O:8])[C:6]2[CH:10]=[CH:11][CH:12]=[C:4]([O:3][C:2]([F:14])([F:13])[F:1])[CH:5]=2)=[CH:23][C:22]=1[C:17]1[N:18]([CH3:21])[N:19]=[CH:20][C:16]=1[Br:15]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5228543-(Trifluoromethoxy)benzoyl chlorideHCID 672655183-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-methyl-2-nitropropoxy)aniline

Product 1

HCID 57814690N-[4-(2-Amino-2-methyl-propoxy)-3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-3-trifluoromethoxy-benzamideYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

3-Trifluoromethoxybenzoyl chloride (12 mg, 0.06 mmol) was added to a solution of 3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-methyl-2-nitropropoxy)aniline (18 mg, 0.05 mmol) and N,N-diisopropylethylamine (10 μl, 0.06 mmol) in dichloromethane (0.5 mL) and the mixture was stirred at room temperature. After 1 h, the solution was diluted with dichloromethane, washed with 1M hydrochloric acid and saturated sodium bicarbonate, dried with sodium sulfate, filtered, and evaporated to dryness. The residue was dissolved in methanol (0.5 mL). Acetic acid (0.1 mL) was added followed by zinc dust (33 mg) and the mixture was stirred at room temperature. After 4 h, the suspension was made basic with ammonium hydroxide and extracted twice with ethyl acetate. The combined extracts were evaporated to dryness, purified by preparative LCMS and lyophilized to give the product (21 mg, 81%) as a TFA-salt. LCMS m/z (%)=529.3 (M+H 81Br 76.1%), 527.5 (M+H 79Br 64.8%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.17 (s, 3 H), 1.18 (s, 3 H), 3.67 (s, 3 H), 3.84 (d, J=9.85 Hz, 1 H), 4.00 (d, J=9.85 Hz, 1 H), 7.30 (d, J=9.09 Hz, 1 H), 7.60-7.65 (m, 1 H), 7.67 (s, 1 H), 7.68-7.73 (m, 2 H), 7.85-7.93 (m, 4 H), 7.95 (dd, J=8.97, 2.65 Hz, 1 H), 8.01 (d, J=7.83 Hz, 1 H), 10.48 (s, 1 H).

Workup

  1. washwashed with 1M hydrochloric acid and saturated sodium bicarbonate
  2. dry with materialdried with sodium sulfate
  3. filtrationfiltered
  4. customevaporated to dryness
  5. dissolutionThe residue was dissolved in methanol (0.5 mL)
  6. additionAcetic acid (0.1 mL) was added
  7. stirringthe mixture was stirred at room temperature
  8. waitAfter 4 h
  9. extractionextracted twice with ethyl acetate
  10. customThe combined extracts were evaporated to dryness
  11. custompurified by preparative LCMS

Sources & evidence

ORD record
ord-82e1efaba2cf4d499e781ec15e97e80f
Source dataset
uspto-grants-2014_03
Patent number
US08664258B2

Reaction notes

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