6-Chloro-3,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazine → 4-(4-chlorophenyl)-1-cyclopropyl-5-(3,8-dimethyl-[1,2,4]-triazolo[4,3-b]pyridazin-6-yl)-3-methyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one

HRID 873983Notes

Reaction equation

HRID 873983 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:15]3[C:14]([CH3:16])=[N:13][N:12]([CH:17]4[CH2:19][CH2:18]4)[C:11]=3[C:10](=[O:20])[NH:9]2)=[CH:4][CH:3]=1.Cl[C:22]1[CH:23]=[C:24]([CH3:32])[C:25]2[N:26]([C:28]([CH3:31])=[N:29][N:30]=2)[N:27]=1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:15]3[C:14]([CH3:16])=[N:13][N:12]([CH:17]4[CH2:19][CH2:18]4)[C:11]=3[C:10](=[O:20])[N:9]2[C:22]2[CH:23]=[C:24]([CH3:32])[C:25]3[N:26]([C:28]([CH3:31])=[N:29][N:30]=3)[N:27]=2)=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 155038066-Chloro-3,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazineHCID 1177027334-(4-chlorophenyl)-1-cyclopropyl-3-methyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one

Product 1

HCID 1177025584-(4-chlorophenyl)-1-cyclopropyl-5-(3,8-dimethyl-[1,2,4]-triazolo[4,3-b]pyridazin-6-yl)-3-methyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one

Procedure

The title compound was prepared in analogy to the procedure described in Example 110 using 4-(4-chlorophenyl)-1-cyclopropyl-3-methyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one (Step 85.6) and 6-chloro-3,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazine (Step 111.2). The crude material was first purified by silica gel column chromatography (EtOAc/MeOH 0.5-1%), followed by preparative achiral SFC (column 4-Ethyl-pyridine, gradient 9-14% in 6 min_total 11 min). tR; 4.66 min (HPLC 1); tR: 1.08 min (LC-MS 2); ESI-MS: 434 [M+H]+ (LC-MS 2); Rf=0.14 (EtOAc); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.04-1.08 (m, 2H) 1.21-1.26 (m, 2H) 1.90 (s, 3H) 2.51 (s, 3H) 2.57 (d, J=1.2 Hz, 3H) 3.82 (dt, J=7.4, 3.7 Hz, 1H) 6.45 (s, 1H) 7.32-7.37 (m, 2H) 7.42-7.47 (m, 2H) 8.08-8.14 (m, 1H).

Workup

  1. customThe crude material was first purified by silica gel column chromatography (EtOAc/MeOH 0.5-1%)
  2. customfollowed by preparative achiral SFC (column 4-Ethyl-pyridine, gradient 9-14% in 6 min_total 11 min)

Sources & evidence

ORD record
ord-b95ae89738cc411f872ab49b1d4c0a8a
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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