Diisopropylethylamine → [2-(4-Chloro-phenyl)-1-methyl-ethyl]-[6-(3,4-dimethoxy-phenyl)-2-methoxy-pyrimidin-4-yl]-amine

HRID 216153Notes

Reaction equation

HRID 216153 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([O:16][CH3:17])[CH:9]=2)[N:5]=[C:4]([O:18][CH3:19])[N:3]=1.C(N(CC)C(C)C)(C)C.[CH3:29][CH:30]([NH2:39])[CH2:31][C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=1.Cl>C1COCC1>[Cl:38][C:35]1[CH:34]=[CH:33][C:32]([CH2:31][CH:30]([NH:39][C:2]2[CH:7]=[C:6]([C:8]3[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([O:16][CH3:17])[CH:9]=3)[N:5]=[C:4]([O:18][CH3:19])[N:3]=2)[CH3:29])=[CH:37][CH:36]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 107161p-Chloroamphetamine hydrochlorideHCID 576361174-Chloro-6-(3,4-dimethoxy-phenyl)-2-methoxy-pyrimidine2×

Product 1

HCID 11524458[2-(4-Chloro-phenyl)-1-methyl-ethyl]-[6-(3,4-dimethoxy-phenyl)-2-methoxy-pyrimidin-4-yl]-amineYield 25.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-chloro-6-(3,4-dimethoxy-phenyl)-2-methoxy-pyrimidine [140 mg, 0.5 mmol, Intermediate (50)] and N,N-diisopropylethylamine (392 μL, 2.25 mmol) in THF (1.7 mL) is added DL-p-chloroamphetamine hydrochloride (154.6 mg, 0.75 mmol, Intermediate (51)]. The mixture is heated to reflux for 2 hours and quenched with water (20 mL) and extracted twice with EtOAc (20 mL). The combined extracts are concentrated and the residue is subjected to flash column chromatography on silica gel eluting with 0 to 50% EtOAc in heptane gradient to afford [2-(4-chloro-phenyl)-1-methyl-ethyl]-[6-(3,4-dimethoxy-phenyl)-2-methoxy-pyrimidin-4-yl]-amine [52.7 mg, 25.5%, Example 43(a)]. LCMS: RT=2.66 minutes, MS: 414 (M+H). 1H NMR (300 MHz, CDCl3): δ 7.65 (1H, d, J=0.066 Hz), 7.53 (1H, dd, J=0.066, 0.028), 7.28 (2H, d, J=0.028 Hz), 7.14 (2H, d, J=0.028 Hz), 6.93 (1H, d, J=0.028 Hz), 6.31 (1H, s), 4.72 (1H, s), 4.34 (1H, s), 4.04 (3H, s), 3.99 (3H, s), 3.95 (3H, s), 2.89 (2H, qd, J=0.045, 0.022 Hz), 1.79 (1H, s), 1.24 (3H, d, J=0.22 Hz). IC50=1726 nM

Workup

  1. temperatureThe mixture is heated
  2. temperatureto reflux for 2 hours
  3. customquenched with water (20 mL)
  4. extractionextracted twice with EtOAc (20 mL)
  5. concentrationThe combined extracts are concentrated

Sources & evidence

ORD record
ord-2694736abe174c43b8a97e59fd3672a4
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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