Acetic Acid → N-[4-(2-Amino-2-methyl-propoxy)-3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-3-trifluoromethyl-benzamide

HRID 521648Notes

Reaction equation

HRID 521648 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6](Cl)=[O:7].C(N(CC)C(C)C)(C)C.[Br:23][C:24]1[CH:28]=[N:27][N:26]([CH3:29])[C:25]=1[C:30]1[CH:31]=[C:32]([CH:34]=[CH:35][C:36]=1[O:37][CH2:38][C:39]([CH3:44])([N+:41]([O-])=O)[CH3:40])[NH2:33].C(O)(=O)C.[OH-].[NH4+]>ClCCl.[Zn]>[NH2:41][C:39]([CH3:44])([CH3:40])[CH2:38][O:37][C:36]1[CH:35]=[CH:34][C:32]([NH:33][C:6](=[O:7])[C:5]2[CH:9]=[CH:10][CH:11]=[C:3]([C:2]([F:13])([F:12])[F:1])[CH:4]=2)=[CH:31][C:30]=1[C:25]1[N:26]([CH3:29])[N:27]=[CH:28][C:24]=1[Br:23]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 14923Ammonium HydroxideHCID 752573-(Trifluoromethyl)benzoyl chlorideHCID 81531DiisopropylethylamineHCID 672655183-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-methyl-2-nitropropoxy)aniline

Product 1

HCID 24888594N-[4-(2-Amino-2-methyl-propoxy)-3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-3-trifluoromethyl-benzamideYield 90%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 3-trifluoromethylbenzoyl chloride (17 μl, 0.11 mmol), N,N-diisopropylethylamine (21 μl, 0.12 mmol) and 3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-methyl-2-nitropropoxy)aniline (37 mg, 0.10 mmol) in 0.5 mL of dichloromethane 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 taken up in methanol (0.4 mL), acetic acid (114 μl, 2.0 mmol) was added followed by zinc dust (65 mg, 1.0 mmol) and the mixture was stirred at room temperature. After 1 h the mixture was made strongly basic with conc ammonium hydroxide, and the product was extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried with sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by preparative LCMS and lyophilized to afford the product (46 mg, 74%) as a TFA-salt. LCMS m/z (%)=513.5 (M+H 81Br 71.7%), 511.3 (M+H 79Br 82.9%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.17 (s, 3H), 1.18 (s, 3H), 3.67 (s, 3H), 3.84 (d, J=9.60 Hz, 1H), 4.00 (d, J=9.85 Hz, 1H), 7.31 (d, J=9.09 Hz, 1H), 7.67 (s, 1H), 7.70 (d, J=2.78 Hz, 1H), 7.80 (t, J=7.71 Hz, 1H), 7.86-7.94 (m, 3H), 7.94-8.01 (m, 2H), 8.26 (d, J=8.08 Hz, 1H), 8.29 (s, 1H), 10.57 (s, 1H).

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. extractionthe product was extracted with ethyl acetate
  6. washThe ethyl acetate layer was washed with brine
  7. dry with materialdried with sodium sulfate
  8. filtrationfiltered
  9. customevaporated to dryness
  10. customThe crude product was purified by preparative LCMS

Sources & evidence

ORD record
ord-f167fbf98fa849f7a9f21b4ef8370e55
Source dataset
uspto-grants-2016_05
Patent number
US09328107B2

Reaction notes

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