Benzoyl chloride, 3-bromo- → N-[4-(2-Amino-2-methyl-propoxy)-3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-3-bromo-benzamide

HRID 1685962Notes

Reaction equation

HRID 1685962 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5](Cl)=[O:6].[Br:11][C:12]1[CH:16]=[N:15][N:14]([CH3:17])[C:13]=1[C:18]1[CH:19]=[C:20]([CH:22]=[CH:23][C:24]=1[O:25][CH2:26][C:27]([CH3:32])([N+:29]([O-])=O)[CH3:28])[NH2:21].C(N(CC)C(C)C)(C)C>ClCCl>[NH2:29][C:27]([CH3:32])([CH3:28])[CH2:26][O:25][C:24]1[CH:23]=[CH:22][C:20]([NH:21][C:5](=[O:6])[C:4]2[CH:8]=[CH:9][CH:10]=[C:2]([Br:1])[CH:3]=2)=[CH:19][C:18]=1[C:13]1[N:14]([CH3:17])[N:15]=[CH:16][C:12]=1[Br:11]

Participants

5

Reactant 3

HCID 74377Benzoyl chloride, 3-bromo-HCID 81531DiisopropylethylamineHCID 672655183-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-methyl-2-nitropropoxy)aniline

Product 1

HCID 57814623N-[4-(2-Amino-2-methyl-propoxy)-3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-3-bromo-benzamideYield 91.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

3-Bromobenzoyl chloride (12 mg, 006 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 (24 mg, 91%) as a TFA-salt. LCMS m/z (%)=525.5 (M+H 81Br2 34.2%), 523.3 (M+H 79Br81Br 100.0%), 521.4 (M+H 79Br212.6%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.16 (s, 3 H), 1.18 (s, 3 H), 3.67 (s, 3 H), 3.83 (d, J=9.60 Hz, 1 H), 3.99 (d, J=9.60 Hz, 1 H), 7.29 (d, J=9.09 Hz, 1 H), 7.51 (t, J=7.83 Hz, 1 H), 7.67 (s, 1H), 7.69 (d, J=2.53 Hz, 1 H), 7.78-7.84 (m, 1 H), 7.84-7.92 (m, 3 H), 7.92-7.98 (m, 2 H), 8.14 (t, J=1.77 Hz, 1 H), 10.44 (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-8c1ed8a7ea2b4e1aa1aeb63a2408f3a8
Source dataset
uspto-grants-2012_04
Patent number
US08148417B2

Reaction notes

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