Cyclopropaneacetic acid → N-((1-(2-(2-cyclopropylacetamido)ethyl)piperidin-4-yl)methyl)-3,5-bis(trifluoromethyl)benzamide

HRID 508633Notes

Reaction equation

HRID 508633 reaction equation
[NH2:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][CH:7]([CH2:10][NH:11][C:12](=[O:27])[C:13]2[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[C:15]([C:23]([F:26])([F:25])[F:24])[CH:14]=2)[CH2:6][CH2:5]1.[CH:28]1([CH2:31][C:32](O)=[O:33])[CH2:30][CH2:29]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O.C(Cl)Cl>[CH:28]1([CH2:31][C:32]([NH:1][CH2:2][CH2:3][N:4]2[CH2:5][CH2:6][CH:7]([CH2:10][NH:11][C:12](=[O:27])[C:13]3[CH:18]=[C:17]([C:19]([F:21])([F:22])[F:20])[CH:16]=[C:15]([C:23]([F:24])([F:25])[F:26])[CH:14]=3)[CH2:8][CH2:9]2)=[O:33])[CH2:30][CH2:29]1

Participants

8

Reactant 4

HCID 138440Cyclopropaneacetic acidHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57993201N-((1-(2-aminoethyl)piperidin-4-yl)methyl)-3,5-bis(trifluoromethyl)benzamide

Product 1

HCID 57993477N-((1-(2-(2-cyclopropylacetamido)ethyl)piperidin-4-yl)methyl)-3,5-bis(trifluoromethyl)benzamide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

A solution of N-((1-(2-aminoethyl)piperidin-4-yl)methyl)-3,5-bis(trifluoromethyl)benzamide (70 mg, 0.18 mmol), TEA (123 μL, 0.881 mmol), and 2-cyclopropylacetic acid (35 mg, 0.35 mmol) in a 1:1 mixture of CH2Cl2:DMF (2 mL) was treated with a solution of HATU (100 mg, 0.264 mmol) in DMF (1 mL). The reaction was stirred over night then transferred to a test tube containing saturated aqueous NaHCO3 (4 mL) and EtOAc (4 mL). The biphasic mixture was mixed vigorously and allowed to separate for 15 min. After separation, the mixture was cooled to −20° C. until the aqueous layer was frozen. The organic layer was then poured off and the solvent was removed under reduced pressure at 50° C. The resulting residue was purified by HiTOPs.

Workup

  1. customthen transferred to a test tube
  2. additionThe biphasic mixture was mixed vigorously
  3. customto separate for 15 min
  4. customAfter separation
  5. temperaturewas frozen
  6. additionThe organic layer was then poured off
  7. customthe solvent was removed under reduced pressure at 50° C
  8. customThe resulting residue was purified by HiTOPs

Sources & evidence

ORD record
ord-9ef1b97f632a4dd689fcb4367352b8c7
Source dataset
uspto-grants-2015_08
Patent number
US09096522B2

Reaction notes

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