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

HRID 474880Notes

Reaction equation

HRID 474880 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-cb6268ed758549148cc556f127a5a54c
Source dataset
uspto-grants-2014_01
Patent number
US08637536B2

Reaction notes

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