6-Bromo-3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridine → 4-(4-chlorophenyl)-1-cyclopropyl-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-3-(methoxymethyl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one

HRID 873988Notes

Reaction equation

HRID 873988 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:15]3[C:14]([CH2:16][O:17][CH3:18])=[N:13][N:12]([CH:19]4[CH2:21][CH2:20]4)[C:11]=3[C:10](=[O:22])[NH:9]2)=[CH:4][CH:3]=1.Br[C:24]1[CH:25]=[C:26]([CH3:34])[C:27]2[N:28]([C:30]([CH3:33])=[N:31][N:32]=2)[CH:29]=1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:15]3[C:14]([CH2:16][O:17][CH3:18])=[N:13][N:12]([CH:19]4[CH2:20][CH2:21]4)[C:11]=3[C:10](=[O:22])[N:9]2[C:24]2[CH:25]=[C:26]([CH3:34])[C:27]3[N:28]([C:30]([CH3:33])=[N:31][N:32]=3)[CH:29]=2)=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 837915436-Bromo-3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridineHCID 1177027014-(4-chlorophenyl)-1-cyclopropyl-3-(methoxymethyl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one

Product 1

HCID 918263314-(4-chlorophenyl)-1-cyclopropyl-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-3-(methoxymethyl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one

Conditions

Temperature
110 °C

Procedure

The title compound was prepared using an analogous procedure to that described in Example 23 using 4-(4-chlorophenyl)-1-cyclopropyl-3-(methoxymethyl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one (Step 130.4) and 6-bromo-3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridine (Step 130.6). The reaction mixture was stirred for 16 h at 110° C. After purification by silica gel column chromatography (CH2Cl2/MeOH 1-5.5%), the resulting residue was purified by SFC (column: PPU, 25 cm, Ø 3 cm, 5 μm, 100 Å; gradient: 12% B for 1 min, 12-17% B in 6 min, 17-50% B in 1 min, 50% B for 1.5 min, 50%-12% B in 1 min, 12% B for 0.5 min; A: scCO2, B: MeOH; flow: 100 mL/min) to provide the title compound (151 mg) as a colorless solid. tR: 0.94 min (LC-MS 2); ESI-MS: 463.1 [M+H]+ (LC-MS 2); Rf=0.37 (CH2Cl2/MeOH 9:1); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.03-1.11 (m, 2H) 1.23-1.31 (m, 2H) 2.42 (s, 3H) 2.61 (s, 3H) 3.06 (s, 3H) 3.84-3.92 (m, 1H) 3.99 (d, J=12.12 Hz, 1H) 4.23 (d, J=12.51 Hz, 1H) 6.46 (s, 1H) 7.28-7.35 (m, 4H) 7.37 (br. s, 1H) 8.48 (br. s, 1H).

Workup

  1. customThe title compound was prepared
  2. customAfter purification by silica gel column chromatography (CH2Cl2/MeOH 1-5.5%)
  3. customthe resulting residue was purified by SFC (column
  4. waitgradient: 12% B for 1 min
  5. wait12-17% B in 6 min
  6. wait17-50% B in 1 min
  7. wait50% B for 1.5 min
  8. wait50%-12% B in 1 min
  9. wait12% B for 0.5 min

Sources & evidence

ORD record
ord-b29c11350a5946949a020c3370964b91
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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