Diisopropylethylamine → cis-2-methoxy-N-(2-pyrrolidin-1-yl-cyclohexyl)-4,6-bis-trifluoromethyl-benzamide

HRID 1950939Notes

Reaction equation

HRID 1950939 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:9]=[C:8]([O:16][CH3:17])[C:4]=1[C:5](O)=[O:6].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.Cl.Cl.[N:55]1([C@H:60]2[CH2:65][CH2:64][CH2:63][CH2:62][C@H:61]2[NH2:66])[CH2:59][CH2:58][CH2:57][CH2:56]1>CN(C)C=O>[CH3:17][O:16][C:8]1[CH:9]=[C:10]([C:12]([F:13])([F:14])[F:15])[CH:11]=[C:3]([C:2]([F:1])([F:18])[F:19])[C:4]=1[C:5]([NH:66][C@@H:61]1[CH2:62][CH2:63][CH2:64][CH2:65][C@@H:60]1[N:55]1[CH2:56][CH2:57][CH2:58][CH2:59]1)=[O:6]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27412872-Methoxy-4,6-bis(trifluoromethyl)benzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66680564cis-2-Pyrrolidin-1-yl-cyclohexylamine dihydrochloride2×

Product 1

HCID 58062981cis-2-methoxy-N-(2-pyrrolidin-1-yl-cyclohexyl)-4,6-bis-trifluoromethyl-benzamideYield 52.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2,4-Bis(trifluoromethyl)-6-methoxy-benzoic acid (200 mg, 0.69 mmol) was dissolved in 5 mL dimethylformamide. N,N-Diisopropyl ethyl amine (359 mg, 2.8 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (264 mg, 0.69 mmol) were added. After 5 minutes of stirring at room temperature cis-2-pyrrolidin-1-yl-cyclohexylamine dihydrochloride (intermediate F) (171 mg, 0.71 mmol) was added. The reaction mixture was stirred at room temperature overnight. The solvent was evaporated off. The residue was taken up in 2N sodium carbonate solution and ethyl acetate and was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (dichloromethane/methanol/ammonia 100:0:0->140:10:1) yielded cis-2-methoxy-N-(2-pyrrolidin-1-yl-cyclohexyl)-4,6-bis-trifluoromethyl-benzamide as a white solid (158 mg, 52%), MS: m/e=439.2 [(M+H)+].

Workup

  1. additionwas added
  2. customThe solvent was evaporated off
  3. extractionethyl acetate and was extracted three times with ethyl acetate
  4. customThe combined organic phases were dried on sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customPurification of the residue by flash chromatography on silica gel (dichloromethane/methanol/ammonia 100:0:0->140:10:1)

Sources & evidence

ORD record
ord-37f47d7b20d841f18a27d2626051152e
Source dataset
uspto-grants-2013_03
Patent number
US08404673B2

Reaction notes

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