3-(Trifluoromethyl)benzylamine → HCID 11548849, compound

HRID 1626190Notes

Reaction equation

HRID 1626190 reaction equation
[CH:1]12[N:7]([CH2:8][CH2:9][O:10][C:11]3[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][C:12]=3[C:18]3[N:19]([CH3:24])[N:20]=[CH:21][C:22]=3[Br:23])[CH:4]([CH2:5][CH2:6]1)[CH2:3][CH2:2]2.C1C([N+]([O-])=O)=CC=C([Cl-][C:35]([O-])=[O:36])C=1.[F:38][C:39]([F:49])([F:48])[C:40]1[CH:41]=[C:42]([CH:45]=[CH:46][CH:47]=1)[CH2:43][NH2:44].C(N(CC)C(C)C)(C)C>ClCCCl>[CH:4]12[N:7]([CH2:8][CH2:9][O:10][C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:35]([NH:44][CH2:43][C:42]4[CH:45]=[CH:46][CH:47]=[C:40]([C:39]([F:48])([F:49])[F:38])[CH:41]=4)=[O:36])=[CH:13][C:12]=3[C:18]3[N:19]([CH3:24])[N:20]=[CH:21][C:22]=3[Br:23])[CH:1]([CH2:2][CH2:3]1)[CH2:6][CH2:5]2

Participants

5

Reactant 3

HCID 759623-(Trifluoromethyl)benzylamineHCID 81531DiisopropylethylamineHCID 58964276HCID 58964276, compound

Product 1

HCID 11548849HCID 11548849, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

4-[2-(7-Aza-bicyclo[2.2.1]hept-7-yl)-ethoxy]-3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-phenylamine (50.0 mg, 0.13 mmol) was added to a solution of 4-nitrophenylchloroformate (26.0 mg, 0.13 mmol) in 1,2-dichloroethane (4.0 mL) and the mixture stirred at room temperature for 1 hour. To the resulting precipitate mixture was added 3-trifluoromethylbenzylamine (0.022 mL, 0.15 mmol) and N,N-diisopropylethylamine (0.030 mL, 0.17 mmol), and the mixture stirred an additional 1 hour. The mixture was concentrated and purified by RP-HPLC. The collected fractions were concentrated and 12% sodium hydroxide (aq) (0.2 mL) was added to give pH 9. The solution was extracted into ethyl acetate and the organic layer was dried over sodium sulfate, filtered, and evaporated to dryness to give a white solid (49 mg, 65%). LCMS m/z (%)=592 (M+H79Br, 100), 594 (M+H81Br, 67). 1H NMR (400 MHz, DMSO-d6) δ: 8.67 (bs, 1H), 7.67 (bs, 1H), 7.65-7.59 (m, 4H), 7.53-7.50 (m, 1H), 7.33 (d, J=2.69 Hz, 1H), 7.12 (d, J=9.04 Hz, 1H), 6.77-6.74 (m, 1H), 4.40 (d, J=4.0 Hz, 2H), 4.08-3.98 (m, 2H), 3.67 (s, 3H), 3.12 (m, 2H), 2.59-2.55 (m, 2H), 1.56-1.54 (m, 4H), 1.17-1.15 (m, 4H).

Workup

  1. stirringthe mixture stirred an additional 1 hour
  2. concentrationThe mixture was concentrated
  3. custompurified by RP-HPLC
  4. concentrationThe collected fractions were concentrated
  5. addition12% sodium hydroxide (aq) (0.2 mL) was added
  6. customto give pH 9
  7. extractionThe solution was extracted into ethyl acetate
  8. dry with materialthe organic layer was dried over sodium sulfate
  9. filtrationfiltered
  10. customevaporated to dryness

Sources & evidence

ORD record
ord-900a75487f3d44b481ff4048c5d2e0d3
Source dataset
uspto-grants-2014_07
Patent number
US08785441B2

Reaction notes

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