N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-N4-methyl-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine → (R)-N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-N4-methyl-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine

HRID 475879Notes

Reaction equation

HRID 475879 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:15]=[C:16]([NH:29][CH3:30])[C:17]4[CH2:22][CH2:21][CH:20]([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)[C:18]=4[N:19]=3)=[CH:9][C:8]=2[O:31][CH3:32])[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:15]=[C:16]([NH:29][CH3:30])[C:17]4[CH2:22][CH2:21][C@H:20]([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)[C:18]=4[N:19]=3)=[CH:9][C:8]=2[O:31][CH3:32])[CH:6]=1

Participants

4

Reactant 1

HCID 50913637N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-N4-methyl-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine

Product 1

HCID 58075673(R)-N2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-N4-methyl-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-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-methyl-7-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine (92 mg, 0.206 mmol from Example 7) was purified using chiral supercritical fluid chromatography (SFC) to afford 28.4 mg of peak A (Example 7A) and 27.4 mg of peak B (Example 7B). SFC Method: Chiralpak OJ-H (30×250 mm, 5 μM), 40% methanol (0.1% diethylamine) in CO2, 35° C., flow rate 70 mL/min for 16 min, absorbance 268 nm, injection 1 mL of 15 mg/mL solution in methanol (multiple stacked injections), tR (peak A)=5.0 min, tR (peak B) 12.3 min. The absolute stereochemistry of individual enantiomers (Examples 7A and 7B) was not determined. LC-MS and 1H NMR analytical data for the separated enantiomers was identical to the racemate (Example 7).

Workup

  1. customwas purified
  2. customto afford 28.4 mg of peak A (Example 7A) and 27.4 mg of peak B (Example 7B)
  3. custom=5.0 min, tR (peak B) 12.3 min

Sources & evidence

ORD record
ord-454e0a8636ed47fb80f016e150566c38
Source dataset
uspto-grants-2014_01
Patent number
US08637525B2

Reaction notes

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