Water → HCID 58075630, compound

HRID 451193Notes

Reaction equation

HRID 451193 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[C:13]2[N:14]=[C:15]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([N:27]4[CH:31]=[N:30][C:29]([CH3:32])=[N:28]4)=[C:23]([O:33][CH3:34])[CH:22]=3)[N:16]=[C:17]([NH:18][CH3:19])[C:12]=2[CH2:11][CH2:10]1.O.C(O)(C(F)(F)F)=O>C(=O)=O.CO>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@H:9]1[C:13]2[N:14]=[C:15]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([N:27]4[CH:31]=[N:30][C:29]([CH3:32])=[N:28]4)=[C:23]([O:33][CH3:34])[CH:22]=3)[N:16]=[C:17]([NH:18][CH3:19])[C:12]=2[CH2:11][CH2:10]1

Participants

6

Reactant 3

HCID 962Water2×HCID 6422Trifluoroacetic acid2×HCID 50914964HCID 50914964, compound

Product 1

HCID 58075630HCID 58075630, compound

Reagents, catalysts & solvents 2

HCID 280Carbon DioxideSolventHCID 887MethanolSolvent4×

Procedure

A racemic mixture of 7-(2,4-difluorophenyl)-N2-(3-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-N4-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine (Example 193) was purified using chiral supercritical fluid chromatography (SFC) to afford peak A (Example 193A) and peak B (Example 193B). SFC Method: Chiralpak OJ-H (30×150 mm), 30% methanol (0.1% diethylamine) in CO2, 100 bar, flow rate 50 mL/min for 12 min, absorbance 268 nm, injection 2.0 mL of 10 mg/mL solution in methanol, tR (peak A)=4.7 min, tR (peak B) 9.6 min. The absolute stereochemistry of individual enantiomers (Examples 193A and 193B) was not determined 193A: LC-MS (M+H)+=446.2. LC Rt 13.03 min (Waters Sunfire 4.6×150 mm 10 to 100% B in A over 15 min, 1.5 mL/min. (A is 90:10:0.1 water:MeOH:TFA; B is 90:10:0.1 MeOH:water:TFA)). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.46 (1H, s), 8.04 (1H, s), 7.51 (1H, d, J=8.55 Hz), 7.04-7.13 (2H, m), 6.78-6.87 (3H, m), 4.42-4.50 (1H, m), 3.68 (3H, s), 3.13 (3H, s), 2.62-2.79 (3H, m), 2.49 (3H, s), 1.96-2.08 (1H, m).

Workup

  1. customwas purified
  2. customto afford peak A (Example 193A) and peak B (Example 193B)
  3. custom=4.7 min, tR (peak B) 9.6 min

Sources & evidence

ORD record
ord-6f4a13b66ced4f96bf254116fd4dd30f
Source dataset
uspto-grants-2013_07
Patent number
US08486952B2

Reaction notes

Loading…