5-(2-Amino-ethyl)-2-(5-trifluoromethyl-pyridin-2-yloxy)benzonitrile → HCID 178432723, compound

HRID 706108Notes

Reaction equation

HRID 706108 reaction equation
[CH3:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10](=[O:17])[N:11]=[C:12](SC)[NH:13][CH:14]=2)=[CH:4][N:3]=1.[NH2:18][CH2:19][CH2:20][C:21]1[CH:22]=[CH:23][C:24]([O:29][C:30]2[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][N:31]=2)=[C:25]([CH:28]=1)[C:26]#[N:27]>C(O)C>[CH3:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10](=[O:17])[N:11]=[C:12]([NH:18][CH2:19][CH2:20][C:21]3[CH:22]=[CH:23][C:24]([O:29][C:30]4[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:37])[F:38])=[CH:32][N:31]=4)=[C:25]([CH:28]=3)[C:26]#[N:27])[NH:13][CH:14]=2)=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 677746445-(2-Amino-ethyl)-2-(5-trifluoromethyl-pyridin-2-yloxy)benzonitrileHCID 178503542HCID 178503542, compound

Product 1

HCID 178432723HCID 178432723, compoundYield 35.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

5-(2-Methyl-pyrimidin-5-ylmethyl)-2-methylsulfanyl-1H-pyrimidin-4-one (50 mg, 0.20 mmol, 1 eq) and 5-(2-Amino-ethyl)-2-(5-trifluoromethyl-pyridin-2-yloxy)-benzonitrile (80 mg, 0.26 mmol, 1.3 eq) were heated at 130° C. (sealed bottle) in 500 μl of absolute ethanol for 24 hours. Solvent was then evaporated and the resulting crude was purified by chromatography on BIOTAGE SP1 purification device using 11 g normal phase silica KP—NH column and DCM/10% MEOH in DCM solvent system (gradient 10-80% of 10% MeOH in DCM in 20 column volumes). Solvent from the gathered fractions of appropriate composition was evaporated and the resulting oil was triturated with hexane to obtain 5-{2-[5-(2-methyl-pyrimidin-5-ylmethyl)-4-oxo-1,4-dihydro-pyrimidin-2-ylamino]-ethyl}-2-(5-trifluoromethyl-pyridin-2-yloxy)-benzonitrile (36 mg, yield=32.4%, purity=92%) in form of tain coloured powder. MS: [M+H]+=508.40. 1H NMR (300 MHz; CDCl3) δ/ppm 2.64 (s, 3H), 2.94 (t, J=7.23 Hz, 2H), 3.53 (s, 2H), 3.57-3.66 (m, 2H), 7.14-7.23 (m, 2H), 7.51 (d, J=8.37 Hz, 2H), 7.55-7.64 (m, 2H), 7.96 (d, J=8.60 Hz, 1H), 8.34 (s, 1H), 8.50 (s, 2H).

Workup

  1. customSolvent was then evaporated
  2. customthe resulting crude was purified by chromatography on BIOTAGE SP1 purification device
  3. customSolvent from the gathered fractions of appropriate composition was evaporated
  4. customthe resulting oil was triturated with hexane

Sources & evidence

ORD record
ord-05a858a106384b4b8d6f604b16300e35
Source dataset
uspto-grants-2015_11
Patent number
US09174968B2

Reaction notes

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