3-Bromo-6-[4-(3-oxetanyl)-1-piperazinyl]pyridazine → (R)-4-((R)-1-((1-cyclopropyl-5-(6-(4-(oxetan-3-yl)piperazin-1-yl)pyridazin-3-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one

HRID 2209101Notes

Reaction equation

HRID 2209101 reaction equation
[CH:1]1([N:4]2[C:8]3[C:9]([O:23][C@@H:24]([C@H:26]4[CH2:30][NH:29][C:28](=[O:31])[CH2:27]4)[CH3:25])=[CH:10][C:11](C4C=CC5OCCNC=5N=4)=[CH:12][C:7]=3[N:6]=[CH:5]2)[CH2:3][CH2:2]1.Br[C:33]1[N:34]=[N:35][C:36]([N:39]2[CH2:44][CH2:43][N:42]([CH:45]3[CH2:48][O:47][CH2:46]3)[CH2:41][CH2:40]2)=[CH:37][CH:38]=1>>[CH:1]1([N:4]2[C:8]3[C:9]([O:23][C@@H:24]([C@H:26]4[CH2:30][NH:29][C:28](=[O:31])[CH2:27]4)[CH3:25])=[CH:10][C:11]([C:33]4[N:34]=[N:35][C:36]([N:39]5[CH2:44][CH2:43][N:42]([CH:45]6[CH2:48][O:47][CH2:46]6)[CH2:41][CH2:40]5)=[CH:37][CH:38]=4)=[CH:12][C:7]=3[N:6]=[CH:5]2)[CH2:2][CH2:3]1

Participants

3

Reactant 2

HCID 1178431703-Bromo-6-[4-(3-oxetanyl)-1-piperazinyl]pyridazineHCID 117843286(R)-4-((R)-1-((1-cyclopropyl-5-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one

Product 1

HCID 117842795(R)-4-((R)-1-((1-cyclopropyl-5-(6-(4-(oxetan-3-yl)piperazin-1-yl)pyridazin-3-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-oneYield 61%

Procedure

Prepared by Suzuki coupling reaction procedure, as previously described for the synthesis of (R)-4-((R)-1-((1-cyclopropyl-5-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one:, using instead 3-bromo-6-(4-(oxetan-3-yl)piperazin-1-yl)pyridazine as a starting material to afford 52.7 mg (61%) of (R)-4-((R)-1-((1-cyclopropyl-5-(6-(4-(oxetan-3-yl)piperazin-1-yl)pyridazin-3-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one:. 1H NMR (300 MHz, d6-DMSO) δ 8.12 (s, 1H), 8.04 (d, J=9.9 Hz, 1H), 7.80 (d, J=1.1 Hz, 1H), 7.62 (m, 2H), 7.35 (d, J=9.9 Hz, 1H), 4.81 (m, 1H), 4.52 (m, 4H), 3.69 (m, 5H), 3.41 (m, 2H), 3.20 (m, 1H), 2.54 (m, 1H), 2.37 (m, 6H), 1.34 (d, J=6.3 Hz, 3H), 1.09 (m, 4H). MS (ESI+) m/z 504.3 (M+H).

Workup

  1. customPrepared by Suzuki
  2. customreaction procedure

Sources & evidence

ORD record
ord-89237519295146598a65cdac849bb5e0
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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