2-Thiophenecarboxaldehyde, 5-chloro- → N-{2-Bromo-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-6-trifluoromethyl-phenyl}-3-cyclohexyl-propionamide

HRID 1820155Notes

Reaction equation

HRID 1820155 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([NH:12][C:13](=[O:22])[CH2:14][CH2:15][CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)=[C:4]([Br:23])[CH:3]=1.[Cl:24][C:25]1[S:29][C:28]([CH:30]=O)=[CH:27][CH:26]=1.C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>CO>[Br:23][C:4]1[CH:3]=[C:2]([NH:1][CH2:30][C:28]2[S:29][C:25]([Cl:24])=[CH:26][CH:27]=2)[CH:7]=[C:6]([C:8]([F:10])([F:11])[F:9])[C:5]=1[NH:12][C:13](=[O:22])[CH2:14][CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

6

Reactant 4

HCID 817002-Thiophenecarboxaldehyde, 5-chloro-HCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 68712206HCID 68712206, compound

Product 1

HCID 11656588N-{2-Bromo-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-6-trifluoromethyl-phenyl}-3-cyclohexyl-propionamideYield 33%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
130 °C

Procedure

N-(4-Amino-2-bromo-6-trifluoromethyl-phenyl)-3-cyclohexyl-propionamide (1.03 g) and 5-chloro-thiophene-2-carbaldehyde (310 uL) were dissolved in methanol (16 mL) and heated to 130° C. for 8 minutes in a sealed microwave process vial. Sodium cyanoborohydride (800 mg) was added and the reaction mixture was heated to 130° C. for 5 minutes in a sealed microwave process vial. Saturated aqueous sodium bicarbonate (100 mL) was added, the product was extracted with ethyl acetate (3×50 mL) and the combined organic phases were washed with water (2×100 mL) and brine (100 mL), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography to furnish 517 mg (33% yield) of the title compound as a yellow solid. LC-MS (m/z) 524 (MH+); tR=4.09, (UV, ELSD) 99%, 99%. 1H NMR (500 MHz, DMSO-d6): 0.86 (q, 2H), 1.15 (m, 3H), 1.26 (m, 1H), 1.46 (q, 2H), 1.65 (m, 5H), 2.24 (t, 2H), 4.89 (d, 2H), 6.94 (d, 1H), 6.95 (d, 1H), 6.98 (d, 1H), 7.04 (t, 1H), 7.13 (d, 1H), 9.32 (s, 1H).

Workup

  1. temperaturethe reaction mixture was heated to 130° C. for 5 minutes in a sealed microwave process vial
  2. extractionthe product was extracted with ethyl acetate (3×50 mL)
  3. washthe combined organic phases were washed with water (2×100 mL) and brine (100 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-27f3aa94091c47fa952293f4cb24d64d
Source dataset
uspto-grants-2009_10
Patent number
US07601870B2

Reaction notes

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