Water → N-(4-Cyclopropylmethanesulfonyl-1-cyclopropylmethyl-cyclohexylmethyl)-2-methyl-6-trifluoromethyl-nicotinamide

HRID 2263608Notes

Reaction equation

HRID 2263608 reaction equation
[CH:1]1([CH2:4][S:5]([CH:8]2[CH2:13][CH2:12][C:11]([CH2:18][NH2:19])([CH2:14][CH:15]3[CH2:17][CH2:16]3)[CH2:10][CH2:9]2)(=[O:7])=[O:6])[CH2:3][CH2:2]1.C(N(C(C)C)C(C)C)C.[CH3:29][C:30]1[N:38]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:36]=[CH:35][C:31]=1[C:32](Cl)=[O:33].O>C(Cl)Cl>[CH:1]1([CH2:4][S:5]([CH:8]2[CH2:13][CH2:12][C:11]([CH2:18][NH:19][C:32](=[O:33])[C:31]3[CH:35]=[CH:36][C:37]([C:39]([F:42])([F:40])[F:41])=[N:38][C:30]=3[CH3:29])([CH2:14][CH:15]3[CH2:16][CH2:17]3)[CH2:10][CH2:9]2)(=[O:7])=[O:6])[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 27756752-Methyl-6-(trifluoromethyl)nicotinoyl chlorideHCID 68681575(1-(Cyclopropylmethyl)-4-((cyclopropylmethyl)sulfonyl)cyclohexyl)methanamine

Product 1

HCID 68684298N-(4-Cyclopropylmethanesulfonyl-1-cyclopropylmethyl-cyclohexylmethyl)-2-methyl-6-trifluoromethyl-nicotinamideYield 51.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of C-(4-cyclopropylmethanesulfonyl-1-cyclopropylmethyl-cyclohexyl)-methylamine (200 mg; 0.701 mmol) and N-ethyldiisopropylamine (0.15 ml; 0.841 mmol) in DCM (5 ml) was added 2-methyl-6-(trifluoromethyl)nicotinoyl chloride (172 mg; 0.771 mmol). The mixture was stirred for 90 minutes. Water (4 ml) and DCM (4 ml) were added and the mixture was stirred vigorously for 5 minutes then passed through a PTFE separation frit. The organic phase was collected and evaporated in vacuo to give an oil. The crude product was chromatographed on silica eluted with 15% EtOAc in DCM to give a yellow oil, which still contained impurities. The oil was rechromatographed on silica eluted with 20% EtOAc in DCM to give a yellow oil. The oil was crystallised from EtOAC using hexane to give a white solid (170 mg). 1H NMR (500 MHz, CDCl3): δ 7.82 (1H, d, J 7.8), 7.55 (1H, d, J 7.9), 5.90 (1H, t, J 6.0), 3.61 (2H, d, J 6.4), 2.98-2.88 (3H, m), 2.72 (3H, s), 2.07-1.85 (6H, m), 1.43-1.37 (2H, m), 1.24 (2H, d, J 6.6), 1.20-1.12 (1H, m), 0.77-0.69 (3H, m), 0.54-0.50 (2H, m), 0.42-0.40 (2H, m), 0.06-0.04 (2H, m). MS (m/e)=473. MPt=148-151° C.

Workup

  1. stirringthe mixture was stirred vigorously for 5 minutes
  2. customthen passed through a PTFE separation frit
  3. customThe organic phase was collected
  4. customevaporated in vacuo
  5. customto give an oil
  6. customThe crude product was chromatographed on silica
  7. washeluted with 15% EtOAc in DCM
  8. customto give a yellow oil, which still contained impurities
  9. customThe oil was rechromatographed on silica
  10. washeluted with 20% EtOAc in DCM
  11. customto give a yellow oil
  12. customThe oil was crystallised from EtOAC

Sources & evidence

ORD record
ord-3b89351f4590418bbe8668630148b3ff
Source dataset
uspto-grants-2010_12
Patent number
US07851638B2

Reaction notes

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