Methylamine → HCID 178485736, compound

HRID 1047382Notes

Reaction equation

HRID 1047382 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][C@H:11]2[CH2:16][CH2:15][C@H:14]([C:17](O)=[O:18])[CH2:13][CH2:12]2)=[CH:6][C:5]=1[C:20]([F:23])([F:22])[F:21])([O-:3])=[O:2].F[P-](F)(F)(F)(F)F.[N:31]1(OC(N(C)C)=[N+](C)C)[C:35]2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.CN>O1CCCC1.CN(C)C=O>[CH3:35][NH:31][C:17]([C@H:14]1[CH2:15][CH2:16][C@H:11]([NH:10][C:7]2[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[C:5]([C:20]([F:23])([F:21])[F:22])[CH:6]=2)[CH2:12][CH2:13]1)=[O:18]

Participants

7

Reactant 4

HCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178525754HCID 178525754, compound

Product 1

HCID 178485736HCID 178485736, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Trans-4-(4-nitro-3-trifluoromethyl-phenylamino)-cyclohexanecarboxylic acid (500 mg, 1.50 mmol, prepared in accordance with Example 42), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (570 mg, 1.5 mmol), and diisopropylethylamine (600 μL, 3.30 mmol) were dissolved in dry tetrahydrofuran (10 mL). The resulting mixture was stirred at room temperature for 10 min, and then cooled to 0° C. A solution of methylamine in tetrahydrofuran (750 μL, 2M, 1.50 mmol) and dimethylformamide (1 mL) was added, and the resulting mixture was stirred at room temperature for 3 hr. The mixture was then concentrated under vacuum. The resulting residue was taken up in dichloromethane (25 mL), and the organic phase was washed with water (10 mL), and then with aqueous saturated hydrogencarbonate (3×10 mL). The organic layer was collected, dried over magnesium sulfate, filtered, and concentrated under vacuum. The residue was diluted in dioxane (5 mL), and a concentrated solution of HCl in dioxane was added (10 mL, 4N). A precipitate formed, which was then washed with diethylether (10 mL) and dried under vacuum. The desired product was isolated as a yellow solid (498 mg, 87% yield).

Workup

  1. temperaturecooled to 0° C
  2. stirringthe resulting mixture was stirred at room temperature for 3 hr
  3. concentrationThe mixture was then concentrated under vacuum
  4. washthe organic phase was washed with water (10 mL)
  5. customThe organic layer was collected
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. additionThe residue was diluted in dioxane (5 mL)
  10. additiona concentrated solution of HCl in dioxane was added (10 mL, 4N)
  11. customA precipitate formed
  12. washwhich was then washed with diethylether (10 mL)
  13. customdried under vacuum

Sources & evidence

ORD record
ord-8a54b4faccb14e3bae45a7ea9038b3da
Source dataset
uspto-grants-2013_10
Patent number
US08569495B2

Reaction notes

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