4-(2-(2,2-Difluorobenzo[D][1,3]dioxol-5-ylamino)pyridin-3-YL)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine → 4-(2-(2,2-Difluorobenzo[d][1,3]dioxol-5-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

HRID 1621623Notes

Reaction equation

HRID 1621623 reaction equation
[F:1][C:2]1([F:44])[O:6][C:5]2[CH:7]=[CH:8][C:9]([NH:11][C:12]3[C:17]([C:18]4[N:23]=[C:22]([CH3:24])[N:21]=[C:20]([N:25](CC5C=CC(OC)=CC=5)CC5C=CC(OC)=CC=5)[N:19]=4)=[CH:16][CH:15]=[CH:14][N:13]=3)=[CH:10][C:4]=2[O:3]1>C(O)(C(F)(F)F)=O>[F:44][C:2]1([F:1])[O:6][C:5]2[CH:7]=[CH:8][C:9]([NH:11][C:12]3[C:17]([C:18]4[N:23]=[C:22]([CH3:24])[N:21]=[C:20]([NH2:25])[N:19]=4)=[CH:16][CH:15]=[CH:14][N:13]=3)=[CH:10][C:4]=2[O:3]1

Participants

3

Reactant 1

HCID 666109184-(2-(2,2-Difluorobenzo[D][1,3]dioxol-5-ylamino)pyridin-3-YL)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 595483914-(2-(2,2-Difluorobenzo[d][1,3]dioxol-5-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amineYield 3.83%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 4-(2-(2,2-difluorobenzo[d][1,3]dioxol-5-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.1352 g, 0.226 mmol) in TFA (8.0 mL) (Aldrich) was heated at 80° C. overnight. The solution was cooled to room temperature and the TFA was removed in vacuo. The residue was treated with a saturated solution of NaHCO3, the aqueous layer was extracted with DCM (3×15 mL), the layers were separated, the combined organic layers were dried and concentrated. The crude brown oil was dissolved in 2.5 mL of DMSO and purified by reversed phase chromatography (Gilson, 10-90% CH3CN in water with NH4OH additive: 0.1% v/v in each solvent). The fractions were concentrated in a Genevac Series II System to give 4-(2-(2,2-difluorobenzo[d][1,3]dioxol-5-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (3.1 mg, 8.65 μmol, 3.83% yield) as a yellow amorphous solid. 1H NMR (400 MHz, d6-DMSO) δ 12.11 (s, 1H); 8.80 (dd, J=7.8, 2.0 Hz, 1H); 8.37 (dd, J=4.6, 2.1 Hz, 1H); 8.15 (d, J=2.2 Hz, 1H); 7.87 (br. s., 1H); 7.77 (br. s., 1H); 7.55 (dd, J=8.8, 2.2 Hz, 1H); 7.35 (d, J=8.8 Hz, 1H); 6.95 (dd, J=7.9, 4.6 Hz, 1H); 2.44 (s, 3H). m/z (ESI, +ve ion) 359.0 (M+H)+.

Workup

  1. customthe TFA was removed in vacuo
  2. additionThe residue was treated with a saturated solution of NaHCO3
  3. extractionthe aqueous layer was extracted with DCM (3×15 mL)
  4. customthe layers were separated
  5. customthe combined organic layers were dried
  6. concentrationconcentrated
  7. dissolutionThe crude brown oil was dissolved in 2.5 mL of DMSO
  8. custompurified by reversed phase chromatography (Gilson, 10-90% CH3CN in water with NH4OH additive
  9. concentrationThe fractions were concentrated in a Genevac Series II System

Sources & evidence

ORD record
ord-7a75e61f38f14acabc31273732a03e7d
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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