N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-N4-ethyl-N4-methyl-8-phenyl-5,6,7,8-tetrahydroquinazoline-2,4-diamine → (R)-N2-(4-(4-Chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-N4-ethyl-N4-methyl-8-phenyl-5,6,7,8-tetrahydroquinazoline-2,4-diamine

HRID 451189Notes

Reaction equation

HRID 451189 reaction equation
[Cl:1][C:2]1[N:3]=[CH:4][N:5]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:23]=[C:22]([N:24]([CH2:26][CH3:27])[CH3:25])[C:21]4[CH2:20][CH2:19][CH2:18][CH:17]([C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=5)[C:16]=4[N:15]=3)=[CH:9][C:8]=2[O:34][CH3:35])[CH:6]=1>C(=O)=O.CO>[Cl:1][C:2]1[N:3]=[CH:4][N:5]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:23]=[C:22]([N:24]([CH2:26][CH3:27])[CH3:25])[C:21]4[CH2:20][CH2:19][CH2:18][C@H:17]([C:28]5[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=5)[C:16]=4[N:15]=3)=[CH:9][C:8]=2[O:34][CH3:35])[CH:6]=1

Participants

4

Reactant 1

HCID 58075270N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-N4-ethyl-N4-methyl-8-phenyl-5,6,7,8-tetrahydroquinazoline-2,4-diamine

Product 1

HCID 58075533(R)-N2-(4-(4-Chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-N4-ethyl-N4-methyl-8-phenyl-5,6,7,8-tetrahydroquinazoline-2,4-diamine

Reagents, catalysts & solvents 2

HCID 280Carbon DioxideSolventHCID 887MethanolSolvent2×

Procedure

A racemic mixture of N2-(4-(4-Chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-N4-ethyl-N4-methyl-8-phenyl-5,6,7,8-tetrahydroquinazoline-2,4-diamine (183 mg, 0.206 mmol from Example 124) was purified using chiral supercritical fluid chromatography (SFC) to afford 54.7 mg of peak A (Example 124A) and 53.3 mg of peak B (Example 124B). SFC Method: Chiralpak OJ-H (30×250 mm, 5 μM), 30% methanol (0.1% diethylamine) in CO2, 35° C., flow rate 70 mL/min for 105 min, absorbance 220 nm, injection 0.75 mL of 26 mg/mL solution in methanol (multiple stacked injections), tR (peak A)=4.9 min, tR (peak B) 12.0 min. The absolute stereochemistry of individual enantiomers (Examples 124A and 124B) were not determined. LC-MS and 1H NMR analytical data for the separated enantiomers was identical to the racemate (Example 124).

Workup

  1. customwas purified
  2. customto afford 54.7 mg of peak A (Example 124A) and 53.3 mg of peak B (Example 124B)
  3. custom=4.9 min, tR (peak B) 12.0 min

Sources & evidence

ORD record
ord-819df4000c224e7989419df0c897f3d5
Source dataset
uspto-grants-2013_07
Patent number
US08486952B2

Reaction notes

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