Dichloromethane → 2-N-Methyl-2-N-phenyl-6-(5-{5-[1-(2,2,2-trifluoroethoxy)ethyl]pyridin-2-yl}-1,2,4-oxadiazol-3-yl)-1,3,5-triazine-2,4-diamine

HRID 341446Notes

Reaction equation

HRID 341446 reaction equation
ClC(Cl)(Cl)CC(=N)O[CH:6]([C:8]1[CH:9]=[N:10][C:11]([C:14]2[O:18][N:17]=[C:16]([C:19]3[N:24]=[C:23]([NH2:25])[N:22]=[C:21]([N:26]([CH3:33])[C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[N:20]=3)[N:15]=2)=[CH:12][CH:13]=1)[CH3:7].[F:37][C:38]([F:42])([F:41])[CH2:39][OH:40].C(Cl)Cl.C(=O)(O)[O-].[Na+]>ClCCCl>[CH3:33][N:26]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[N:22]=[C:23]([NH2:25])[N:24]=[C:19]([C:16]2[N:15]=[C:14]([C:11]3[CH:12]=[CH:13][C:8]([CH:6]([O:40][CH2:39][C:38]([F:42])([F:41])[F:37])[CH3:7])=[CH:9][N:10]=3)[O:18][N:17]=2)[N:20]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 64092,2,2-TrifluoroethanolHCID 516892Sodium BicarbonateHCID 668027621-[6-(3-{4-Amino-6-[methyl(phenyl)amino]-1,3,5-triazin-2-yl]-1,2,4-oxadiazol-5-yl)pyridin-3-yl}ethyl 2,2,2-trichloroethanecarboximidate2×

Product 1

HCID 668025842-N-Methyl-2-N-phenyl-6-(5-{5-[1-(2,2,2-trifluoroethoxy)ethyl]pyridin-2-yl}-1,2,4-oxadiazol-3-yl)-1,3,5-triazine-2,4-diamineYield 5%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

1-[6-(3-{4-Amino-6-[methyl(phenyl)amino]-1,3,5-triazin-2-yl}-1,2,4-oxadiazol-5-yl)pyridin-3-yl]ethyl 2,2,2-trichloroethanecarboximidate (Intermediate 139, 0.497 g, 0.93 mmol) was suspended in DCE (8 mL). 2,2,2-Trifluoroethanol (0.669 mL, 9.29 mmol) and tetrafluoroboric acid diethyl ether complex (0.025 mL, 0.19 mmol) were added and the mixture was stirred at room temperature for 7 h. LCMS showed incomplete conversion, so further tetrafluoroboric acid diethyl ether complex (0.125 mL, 0.93 mmol) was added and the mixture stirred at room temperature for 21 h. DCM (100 mL) and saturated aq. sodium bicarbonate (50 mL) were added. The organic layer was separated, washed with brine (30 mL), dried over sodium sulfate and concentrated under vacuum to yield a brown solid, which was purified by FCC using a gradient of 0-5% MeOH in DCM. The crude product was then purified by preparative HPLC, Method D, to afford an off-white solid. This was further purified by FCC using a gradient of 0-3% MeOH in DCM to afford the title compound as an off-white solid (0.022 g, 5%).

Workup

  1. additionwas added
  2. stirringthe mixture stirred at room temperature for 21 h
  3. customThe organic layer was separated
  4. washwashed with brine (30 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customto yield a brown solid, which
  8. customwas purified by FCC
  9. customThe crude product was then purified by preparative HPLC, Method D
  10. customto afford an off-white solid
  11. customThis was further purified by FCC

Sources & evidence

ORD record
ord-b73c1318d0f44cc4854e9cb171151fdc
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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