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

HRID 2110681Notes

Reaction equation

HRID 2110681 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-1a704cf096ac49329541fd1db475140e
Source dataset
uspto-grants-2009_04
Patent number
US07517889B2

Reaction notes

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